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Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03499353
Recruitment Status : Terminated (This study was terminated based on Pfizer's change in clinical development strategy not related to safety and efficacy.)
First Posted : April 17, 2018
Results First Posted : November 9, 2021
Last Update Posted : November 9, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
A PHASE 2, NON RANDOMIZED, OPEN LABEL, SINGLE ARM, MULTI CENTER STUDY OF TALAZOPARIB FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER

Condition or disease Intervention/treatment Phase
Early Breast Cancer Drug: TALAZOPARIB Phase 2

Detailed Description:
TALAZOPARIB (PARP INHIBITOR) FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER. THIS IS A MONOTHERAPY TREATMENT FOR 24 WKS FOLLOWED BY SURGERY TO EVALUATE PATHOLOGICAL COMPLETE RESPONSE.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: THIS IS AN OPEN LABEL SINGLE ARM STUDY
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 2, NON RANDOMIZED, OPEN LABEL, SINGLE ARM, MULTI CENTER STUDY OF TALAZOPARIB FOR NEOADJUVANT TREATMENT OF GERMLINE BRCA1/2 MUTATION PATIENTS WITH EARLY HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE BREAST CANCER
Actual Study Start Date : August 27, 2018
Actual Primary Completion Date : September 23, 2020
Actual Study Completion Date : September 23, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: TALAZOPARIB
SINGLE ARM, NON-RANDOMIZED
Drug: TALAZOPARIB
Talazoparib 1mg/day




Primary Outcome Measures :
  1. Percentage of Participants Achieving Pathological Complete Response (pCR) as Per Independent Central Review (ICR) in Evaluable Analysis Set as Per ICR With 80% Confidence Interval (CI) [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current American Joint Committee on Cancer [AJCC] staging system). pCR rate by ICR was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

  2. Percentage of Participants Achieving pCR as Per ICR in Evaluable Analysis Set as Per ICR With 95% CI [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving pCR as Per ICR in Intention-to-Treat (ITT) Analysis Set With 80% CI [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

  2. Percentage of Participants Achieving pCR as Per ICR in ITT Analysis Set With 95% CI [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

  3. Percentage of Participants Achieving pCR as Per Investigator in Evaluable Analysis Set as Per Investigator [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by investigator was defined as the percentage of participants achieving pCR by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per Investigator). The exact CI was calculated using the Blaker's method.

  4. Percentage of Participants Achieving pCR as Per Investigator in ITT Analysis Set [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ie, ypT0/Tis ypN0 in the current AJCC staging system). pCR rate by investigator in ITT Analysis Set was defined as the percentage of participants achieving pCR by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

  5. Percentage of Participants Achieving pCR in Breast Only as Per Investigator in Evaluable Analysis Set as Per Investigator [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by investigator was defined as the percentage of participants achieving pCR in breast by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per Investigator). The exact CI was calculated using the Blaker's method.

  6. Percentage of Participants Achieving pCR in Breast Only as Per Investigator in ITT Analysis Set [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by investigator in ITT Analysis Set was defined as the percentage of participants achieving pCR in breast by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

  7. Percentage of Participants Achieving pCR in Breast Only as Per ICR in Evaluable Analysis Set as Per ICR [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by ICR was defined as the percentage of participants achieving pCR in breast by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the evaluable population (Evaluable Analysis Set as per ICR). The exact CI was calculated using the Blaker's method.

  8. Percentage of Participants Achieving pCR in Breast Only as Per ICR in ITT Analysis Set [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    pCR in breast was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes on hematoxylin and eosin evaluation of the complete resected breast specimen following completion of neoadjuvant therapy with talazoparib. pCR rate in breast by ICR in ITT Analysis Set was defined as the percentage of participants achieving pCR in breast by ICR after talazoparib treatment for 24 weeks, followed by surgery, among all participants in the ITT Analysis Set. The exact CI was calculated using the Blaker's method.

  9. Percentage of Participants With Residual Cander Burden (RCB) as Per ICR in Evaluable Analysis Set as Per ICR [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    The RCB is a continuous index derived from the following: primary tumor dimensions; cellularity of the tumor bed; axillary nodal burden. Residual cancer burden by ICR is reported as a categorical variable with four classes (categories): RCB 0 (pCR), I (minimal RCB), II (moderate RCB), III (extensive RCB). Participants who had progressive disease or was unable to be assessed for RCB due to missing required axillary specimen were counted in the "Missing" category. The simultaneous exact CI was calculated using Goodman's method.

  10. Percentage of Participants With RCB as Per ICR in ITT Analysis Set [ Time Frame: Date of surgery (maximum of approximately 8 months post-baseline) (assessed within a maximum of 6 weeks of last dose of talazoparib) ]
    The RCB is a continuous index derived from the following: primary tumor dimensions; cellularity of the tumor bed; axillary nodal burden. Residual cancer burden by ICR is reported as a categorical variable with four classes (categories): RCB 0 (pCR), I (minimal RCB), II (moderate RCB), III (extensive RCB). Participants who had progressive disease or was unable to be assessed for RCB due to missing required axillary specimen were counted in the "Missing" category. The simultaneous exact CI was calculated using Goodman's method.

  11. Probability of Being Event-Free at 3 Years in Evaluable Analysis Set [ Time Frame: 3 years after surgery ]
    Event-Free Survival (EFS) is defined as the time from surgery date to first documentation of local or distant recurrence or death or initiation of antineoplastic therapy before documentation of first relapse. Participants discontinuing study before documentation of first relapse or death, but after surgery were censored observations for EFS. EFS at 3 years is defined as the probability of being event free at 3 years after surgery using Kaplan Meier methods.

  12. Probability of Being Alive at 3 Years in Evaluable Analysis Set [ Time Frame: 3 years after first dose of talazoparib ]
    Overall Survival (OS) is defined as the time from first dose of talazoparib to death due to any cause. Participants not known to have died at the time of the analysis were right censored on the date they were last known to be alive before the analysis data cutoff date. OS at 3 years is defined as the probability of being alive at 3 years after first dose of talazoparib using Kaplan Meier methods.

  13. Probability of Being Alive at 3 Years in ITT Analysis Set [ Time Frame: 3 years after first dose of talazoparib ]
    OS is defined as the time from first dose of talazoparib to death due to any cause. Participants not known to have died at the time of the analysis were right censored on the date they were last known to be alive before the analysis data cutoff date. OS at 3 years is defined as the probability of being alive at 3 years after first dose of talazoparib using Kaplan Meier methods.

  14. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs that occurred between first dose of study drug and up to 28 days after the last dose that were absent before treatment or worsened relative to pretreatment state. Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE.

  15. Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.

  16. Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Drug [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred between first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pretreatment state.

  17. Number of Participants With TEAEs Leading to Temporary Discontinuation of Study Drug [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred between first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pretreatment state.

  18. Number of Participants With TEAEs Leading to Dose Reduction of Study Drug [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred between first dose of study drug and up to 28 days after the last dose that were absent before treatment or that worsened relative to pretreatment state.

  19. Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    Laboratory parameters included hematology, serum chemistry, urinalysis and coagulation. Grades of laboratory abnormalities were defined according to NCI CTCAE version 4.03. Participants with laboratory test abnormalities meeting specified criteria (>upper limit of normal [ULN] or <lower limit of normal [LLN]) (without regards to baseline abnormality) are reported.

  20. Number of Participants With Hematology Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    Hematology laboratory parameters included hematocrit, hemoglobin, mean corpuscular volume, red blood cells, platelets, white blood cells with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils). Grades of lab results were defined by NCI CTCAE version 4.03. Grade 1(mild)=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE. This outcome measure was based only on laboratory data. As Grade 4 anemia cannot be assessed based only on laboratory data, it was not applicable for analysis in this outcome measure.

  21. Number of Participants With Chemistry Laboratory Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline [ Time Frame: Baseline to 28 days after the last dose of talazoparib (maximum of approximately 8 months) ]
    Chemistry laboratory parameters included albumin, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, non-fasting glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and lactate dehydrogenase. Grades of laboratory results were defined by NCI CTCAE version 4.03. Grade 1 (Mild) = asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 (Moderate ) = minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3 = severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4 = events with life-threatening consequences, urgent intervention indicated; Grade 5 = death related to AE.

  22. Trough Plasma Concentration (Ctrough) of Talazoparib in Cycles 2, 3 and 4 in PK Analysis Set [ Time Frame: Pre-dose on Day 1 of Cycles 2, 3, 4 ]
  23. Within-Participant Average Ctrough of Talazoparib at Steady State in PK Analysis Set [ Time Frame: Pre-dose on Day 1 of Cycles 2, 3, 4 ]
    Within-participant average Ctrough of talazoparib at steady state for each participant was defined as the average (mean) value of the steady state Ctrough values (Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1 trough concentrations) for each individual participant.

  24. Ctrough of Talazoparib in Cycles 2, 3 and 4 in Dose-Compliant PK Analysis Set [ Time Frame: Pre-dose on Day 1 of Cycles 2, 3, 4 ]
  25. Within-Participant Average Ctrough of Talazoparib at Steady State in Dose-Compliant PK Analysis Set [ Time Frame: Pre-dosing on Day 1 of Cycles 2, 3, 4 ]
    Within-participant average Ctrough of talazoparib at steady state for each participant was defined as the average (mean) value of the steady state Ctrough values (Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1 trough concentrations) for each individual participant.

  26. Number of Participants Who Achieved Definitive Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Per European Organization For Research And Treatment Of Cancer Quality Of Life Questionnaire (EORTC QLQ-30) [ Time Frame: Baseline to End of Treatment visit (assessed for maximum of 33 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes (PROs), consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point decrease from baseline without any subsequent <10 point decrease.


  27. Kaplan-Meier Estimate of Time to Definitive Deterioration in GHS/QoL Per EORTC QLQ-30 [ Time Frame: Baseline to End of Treatment visit (assessed for maximum of 33 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point decrease from baseline without any subsequent <10 point decrease.


  28. Probability of Not Achieving Definitive Deterioration in GHS/QoL Per EORTC QLQ-C30 at 3 and 6 Months [ Time Frame: 3 months and 6 months post-baseline ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all to 4=very much).

    For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point decrease from baseline without any subsequent <10 point decrease.

    Probability of not achieving definitive deterioration (being event-free) at specified time points (3 and 6 months post-baseline) using the Kaplan Meier method were reported.


  29. Number of Participants Who Achieved Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline to End of Treatment visit (assessed for maximum of 33 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point increase from baseline without any subsequent <10 point increase.


  30. Kaplan-Meier Estimate of Time to Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline to End of Treatment visit (assessed for maximum of 33 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as ≥10 point increase from baseline without any subsequent <10 point increase.


  31. Probability of Not Achieving Definitive Deterioration in Nausea and Vomiting Symptoms Per EORTC QLQ-C30 at 3 and 6 Months [ Time Frame: 3 months and 6 months post-baseline ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, with 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores (1=very poor to 7=excellent); other items have 4 possible scores (1=not at all to 4=very much).

    For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A linear transformation was applied to raw scores so that transformed scores lie between 0 to 100, with 0 being the best and 100 being the worst for this symptom scale. A 10 point change from baseline was used to indicate clinically meaningful change. Definitive deterioration was defined as≥10 point increase from baseline without any subsequent <10 point increase. Probability of not achieving definitive deterioration (being event-free) at specified time points (3 and 6 months post-baseline) using Kaplan Meier method were reported.


  32. Change From Baseline in Global QoL Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the GHS/QoL scale, participants rated their overall health and quality of life within the past week. Negative change from baseline indicates deterioration in GHS/QoL and positive change indicates improvement.


  33. Change From Baseline in Physical Functioning Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the physical functioning scale, participants self-rated levels of difficulty in doing strenuous activities, taking a walk, how much they needed to stay in bed or a chair, or needed help with eating, dressing, bathing, using the toilet. Negative change from baseline indicates deterioration in physical functioning and positive change indicates improvement.


  34. Change From Baseline in Role Functioning Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the role functioning scale, participants self-rated how much they were limited in doing work or daily activities, or in pursuing hobbies or other leisure time activities during the past week. Negative change from baseline values indicates deterioration in role functioning and positive change indicates improvement.


  35. Change From Baseline in Emotional Functioning Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the emotional functioning scale, participants self-rated how much they felt tense, worried, irritable or depressed during the past week. Negative change from baseline values indicates deterioration in emotional functioning and positive change indicates improvement.


  36. Change From Baseline in Cognitive Functioning Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the cognitive functioning scale, participants self-rated the extent of difficulty in concentrating on things or remembering things during the past week. Negative change from baseline values indicates deterioration in cognitive functioning and positive change indicates improvement.


  37. Change From Baseline in Social Functioning Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the social functioning scale, participants self-rated how much their physical condition or medical treatment interfered with their family life and social activities during the past week. Negative change from baseline values indicates deterioration in social functioning and positive change indicates improvement.


  38. Change From Baseline in Fatigue Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the fatigue symptoms scale, participants self-rated how much they had felt weak, tired or needed to rest during the past week. Negative change from baseline values indicates improvement of fatigue symptoms and positive change indicates deterioration.


  39. Change From Baseline in Nausea and Vomiting Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. Negative change from baseline values indicates improvement of nausea and vomiting symptoms and positive change indicates deterioration.


  40. Change From Baseline in Pain Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the pain symptoms scale, participants self-rated the extent of pain and how much the pain interfered with daily activities during the past week. Negative change from baseline values indicates improvement of pain symptoms and positive change indicates deterioration.


  41. Change From Baseline in Dyspnoea Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the dyspnoea symptoms scale, participants self-rated the intensity of shortness of breath during the past week. Negative change from baseline values indicates improvement of dyspnoea symptoms and positive change indicates deterioration.


  42. Change From Baseline in Insomnia Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the insomnia symptoms scale, participants self-rated the intensity of shortness of breath during the past week. Negative change from baseline values indicates improvement of insomnia symptoms and positive change indicates deterioration.


  43. Change From Baseline in Appetite Loss Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the appetite loss symptoms scale, participants self-rated the extent of lack of appetite during the past week. Negative change from baseline values indicates improvement of appetite loss symptoms and positive change indicates deterioration.


  44. Change From Baseline in Constipation Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the constipation symptoms scale, participants self-rated the intensity of constipation during the past week. Negative change from baseline values indicates improvement of constipation symptoms and positive change indicates deterioration.


  45. Change From Baseline in Diarrhea Symptoms Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the diarrhea symptoms scale, participants self-rated the intensity of diarrhea during the past week. Negative change from baseline values indicates improvement of diarrhea symptoms and positive change indicates deterioration.


  46. Change From Baseline in Financial Difficulties Per EORTC QLQ-C30 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the symptom scale of financial difficulties, participants self-rated how much their physical condition or medical treatment caused financial difficulties. Negative change from baseline values indicates improvement of financial difficulties and positive change indicates deterioration.


  47. Change From Baseline in Body Image Per EORTC QLQ Breast Cancer Quality of Life Questionnaire (EORTC QLQ-BR23) [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the functional scale of body image, participants self-rated how much they felt physically less attractive or less feminine, difficult to look at themselves naked, or dissatisfied with their body during the past week. Negative change from baseline indicates worsening of self-rated body image and positive change indicates improvement.


  48. Change From Baseline in Sexual Functioning Per EORTC QLQ-BR23 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the sexual functioning scale, participants self-rated to what extent they were interested in sex and were sexually active (with or without intercourse) during the past 4 weeks. Negative change from baseline values indicates worsening of sexual functioning and positive change indicates improvement.


  49. Change From Baseline in Sexual Enjoyment Per EORTC QLQ-BR23 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the functional scale of sexual enjoyment, participants self-rated to what extent sex was enjoyable for them during the past 4 weeks. Negative change from baseline values indicates worsening of sexual enjoyment and positive change indicates improvement.


  50. Change From Baseline in Future Perspective Per EORTC QLQ-BR23 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the functional scale of future perspective, participants self-rated how much they were worried about their health in the future. Negative change from baseline values indicates worsening of future perspective and positive change indicates improvement.


  51. Change From Baseline in Systemic Therapy Side Effects Per EORTC QLQ-BR23 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the systemic therapy side effects scale, participants self-rated the intensity of symptoms of dry mouth, unusual taste, pain and irritation of eyes, hair loss, feeling ill or unwell, hot flushes and headaches during the past week. Negative change from baseline= improvement of these side effects, positive change = deterioration.


  52. Change From Baseline in Breast Symptoms Per EORTC QLQ-BR23 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the breast symptoms scale, participants self-rated how much they had pain or skin problems (e.g. itchy, dry, flaky) on or in the area of affected breast, and how much this area was swollen or oversensitive during the past week. Negative change from baseline indicates improvement of breast symptoms and positive change indicates deterioration.


  53. Change From Baseline in Arm Symptoms Per EORTC QLQ-BR23 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the arm symptoms scale, participants self-rated how much they had pain in the arm or shoulder, how much the arm or hand was swollen, and difficulty in raising the arm or moving it sideways. Negative change from baseline indicates improvement of arm symptoms and positive change indicates deterioration.


  54. Change From Baseline in Upset by Hair Loss Per EORTC QLQ-BR23 [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]

    EORTC-QLQ-BR23 is a 23-item breast cancer module developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer, consisting of 2 functional scales, 3 symptoms scales, and 3 single-item scales. Each scale has 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for functional scales, and 0 being the best and 100 being the worst for symptoms scales.

    For the upset by hair loss scale, participants self-rated how upset they were due to loss of hair during the past week. Negative change from baseline values indicates improvement of upset by hair loss and positive change indicates deterioration.


  55. Number of Participants With Deterioration in Nausea/Vomiting Symptoms [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]
    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Deterioration in nausea and vomiting symptoms was defined as a 10 point or more increase from baseline for that specific time point.

  56. Number of Participants With Improvement in Nausea/Vomiting Symptoms [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]
    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. Improvement in nausea and vomiting symptoms was defined as a 10 point or more decrease from baseline for that specific time point.

  57. Number of Participants With No Change in Nausea/Vomiting Symptoms [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]
    EORTC QLQ-C30 is a 30-item cancer-specific instrument that assesses participant reported outcomes, consisting of 5 functional scales, 3 symptoms scales, a GHS/QoL scale, and 6 single-item scales. The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all to 4=very much). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100, with 0 being the worst and 100 being the best for GHS/QoL and functional scales, and 0 being the best and 100 being the worst for symptoms scales. For the nausea and vomiting symptoms scale, participants self-rated how much they had felt nauseated and/or vomited during the past week. A 10 point change from baseline was used to indicate clinically meaningful change. No change in nausea/vomiting symptoms=having neither deterioration (≥10 point increase from baseline) nor improvement (≥10 point decrease from baseline) for the time point.

  58. Number of Participants With Missed Expected Menstrual Periods Per Patient Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day 1 of Cycles 3-6, End of Treatment visit (maximum of 33 weeks) and Post-surgical follow-up visit (maximum of 41 weeks) ]
    Missed expected menstrual period was assessed electronically using the PRO CTCAE questionnaire, a PRO measure developed to evaluate symptomatic toxicity in patients on cancer clinical trials. This objective captures the concept of fertility preservation through PRO, since there is a possible fertility sparing effect of talazoparib versus chemotherapy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Germline BRCA 1/2 Mutation Positive
  • Women and men at least 18 years of age or older.
  • Histologically confirmed invasive adenocarcinoma of the breast
  • HER2 negative breast cancer as defined by ASCO-CAP criteria
  • Tumor greater than or equal toT1, N0-3
  • No evidence of distant metastasis
  • Adequate bone marrow, hepatic, and renal function
  • ECOG performance status 0 or 1

Exclusion Criteria:

  • Any other previous antitumor therapies for the current cancer event. Treatment for ductal carcinoma in situ (DCIS) is allowed; ie, surgery, hormonal therapy and radiation.
  • Evidence of distant metastasis apparent prior to randomization
  • Patients with inflammatory breast carcinoma
  • Malignancy within the last 3 years, except: Stage 1 melanoma which does not require any further treatment after adequate surgical excision; adequately treated non melanoma skin cancer; Curatively treated in situ cancer of the cervix; Stage 1, Grade 1 endometrial carcinoma; or Adequately treated contralateral breast carcinoma which has been disease free for a year; Other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for 5 years.
  • Previous or concomitant systemic anti cancer therapies used for the treatment of cancer in the last 3 years.
  • Prior treatment with a PARP inhibitor in any disease setting
  • Concomitant use of Strong P gp inhibitors or inducers or BCRP inhibitors
  • Patients who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol
  • Major surgery within 14 days prior to study entry
  • Known history of cardiac disease, for example : Myocardial infarction or symptomatic cardiac ischemia within 24 weeks before screening; Congestive heart failure New York Heart Association Class III or IV; History of clinically significant ventricular arrhythmias within one year prior to randomization; History of Mobitz II second degree or third degree heart block, uncontrolled hypertension.
  • Active clinically significant infection
  • Clinically significant bleeding diathesis or coagulopathy
  • Non healing wound, ulcer or bone fracture
  • Known hypersensitivity to any of the components of talazoparib
  • Patients with myelodysplastic syndrome/acute myeloid leukemia
  • Patients with uncontrolled seizures.
  • Any evidence of other disease or any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03499353


Locations
Show Show 97 study locations
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] August 14, 2019
Statistical Analysis Plan  [PDF] February 26, 2020

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03499353    
Other Study ID Numbers: C3441020
TALAZOPARIB NEOADJ BC ( Other Identifier: Alias Study Number )
First Posted: April 17, 2018    Key Record Dates
Results First Posted: November 9, 2021
Last Update Posted: November 9, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Neoadjuvant Therapy, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 NEGATIVE Breast Cancer, BRCA Positive
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents