Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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
Last Update Posted : March 24, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE April 9, 2018
First Posted Date  ICMJE April 17, 2018
Last Update Posted Date March 24, 2021
Actual Study Start Date  ICMJE August 27, 2018
Actual Primary Completion Date September 23, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
Pathological Complete Response (pCR) by Independent Central Reviewer(ICR) [ Time Frame: Following the completion of 24 weeks of Talazoparib Treatment ]
Pathological Complete Response(pCR) by Independent Central Reviewer (ICR) defined by: defined as ypT0/Tis ypN0 (the absence of residual invasive cancer in the breast and the axillary lymph nodes on evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy).
Original Primary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
Pathological Complete Response (pCR) by Independent Central Reviewer(ICR) [ Time Frame: Following the completion of 24 weeks of Talazoparib Treatment ]
Pathological Complete Response(pCR) by Independent Central Reviewer (ICR) defined by: defined as ypT0, ypN0 (the absence of residual invasive and in situ cancer on evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
  • pCR by Investigator [ Time Frame: Following the completion of 24 weeks of Talazoparib Treatment ]
    pCR rate by investigator is defined as the number and percentage of patients achieving pCR by investigator review after talazoparib treatment for 24 weeks, followed by surgery, among all patients in the evaluable population.
  • Residual Cancer Burden(RCB) by Independent reviewer [ Time Frame: Following the completion of 24 weeks of Talazoparib Treatment ]
    Residual cancer burden by ICR will be reported as a categorical variable with four classes (categories) RCB 0 (pCR), I (minimal RCB), II (moderate RCB), and III (extensive RCB).
  • pCR by independent Reviewer in Breast [ Time Frame: Following the completion of 24 weeks of Talazoparib Treatment ]
    pCR rate in breast by ICR is defined as the number and percentage of patients achieving pCR in breast by independent central review after talazoparib treatment for 24 weeks, followed by surgery, among all patients in the evaluable population
  • Event Free Survival [ Time Frame: Time of Surgery up to 36 months ]
    Time of surgery to first documentation of local or distant recurrence, or death or initiation of antineoplastic therapy before documentation of first relapse
  • Overall Survival [ Time Frame: First Dose of Talazoparib up to 42 months ]
    Time from the first dose of Talazoparib to death due to any cause
  • Incidence of Adverse Events [ Time Frame: Upon signing Informed Consent up to 42 months ]
    Type, incidence, severity (as graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v4.03), seriousness and relationship of study medications to adverse events (AE) and any laboratory abnormalities
  • Patient Reported Outcome: Deterioration of Global Health Status [ Time Frame: First dose of Talazoparib up to 9 months ]
    Time to definitive deterioration of Global Health Status per EORTC QLQ-C30
  • Patient Reported Outcome: Nausea and vomiting symptoms [ Time Frame: First dose of Talazoparib up to 9 months ]
    Time to definitive deterioration in nausea and vomiting symptoms per EORTC QLQ C30
  • Patient Reported Outcome: global health status/QoL, functioning, and symptoms [ Time Frame: First dose of Talazoparib up to 9 months ]
    Change from baseline in global health status/QoL, functioning, and symptoms per EORTC QLQ C30 and EORTC QLQ BR 23
  • Patient Reported Outcome- Antiemetic Log [ Time Frame: First dose of Talazoparib up to 9 months ]
    Proportion of patients with deterioration, improvement and no change in nausea and vomiting symptoms.
  • Patient Reported Outcome: Missed Menstrual Period [ Time Frame: First dose of Talazoparib up to 9 months ]
    Change from baseline in proportion of patients with missed expected menstrual period per PRO CTCAE
  • Pharmacokenetic assessment of Talazoparib [ Time Frame: week 4, week 8, week 12 ]
    Plasma concentration of talazoparib
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Talazoparib For Neoadjuvant Treatment Of Germline BRCA1/2 Mutation Patients With Early Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer
Official Title  ICMJE 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
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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Early Breast Cancer
Intervention  ICMJE Drug: TALAZOPARIB
Talazoparib 1mg/day
Study Arms  ICMJE Experimental: TALAZOPARIB
SINGLE ARM, NON-RANDOMIZED
Intervention: Drug: TALAZOPARIB
Publications * Litton JK, Scoggins ME, Hess KR, Adrada BE, Murthy RK, Damodaran S, DeSnyder SM, Brewster AM, Barcenas CH, Valero V, Whitman GJ, Schwartz-Gomez J, Mittendorf EA, Thompson AM, Helgason T, Ibrahim N, Piwnica-Worms H, Moulder SL, Arun BK. Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. J Clin Oncol. 2020 Feb 10;38(5):388-394. doi: 10.1200/JCO.19.01304. Epub 2019 Aug 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 23, 2020)
61
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2018)
122
Actual Study Completion Date  ICMJE September 23, 2020
Actual Primary Completion Date September 23, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03499353
Other Study ID Numbers  ICMJE C3441020
TALAZOPARIB NEOADJ BC ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP