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A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4]

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: NCT02297438
Recruitment Status : Active, not recruiting
First Posted : November 21, 2014
Results First Posted : November 18, 2021
Last Update Posted : January 31, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The study is designed to compare the clinical benefit following treatment with letrozole in combination with Palbociclib versus letrozole in combination with placebo in Asian postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: Palbociclib Drug: Letrozole Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 340 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A MULTICENTER, RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDY OF PALBOCICLIB (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF PREVIOUSLY UNTREATED ASIAN POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) ADVANCED BREAST CANCER
Actual Study Start Date : March 23, 2015
Actual Primary Completion Date : August 31, 2020
Estimated Study Completion Date : December 2, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Palbociclib + Letrozole
Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously)
Drug: Palbociclib
Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
Other Name: PD-0332991

Drug: Letrozole
Letrozole, 2.5mg, orally once daily (continuously)

Active Comparator: Placebo + Letrozole
Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).
Drug: Placebo
Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Drug: Letrozole
Letrozole, 2.5mg, orally once daily (continuously)




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) Based on Investigator's Assessment [ Time Frame: Randomization up to 65 months ]
    PFS was based on Kaplan-Meier estimates. PFS was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. In this outcome measure, PFS was based on investigator's assessment.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) [ Time Frame: Randomization up to 65 months ]
    PFS was based on Kaplan-Meier estimates. PFS was defined as time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause in the absence of documented progressive disease, whichever occurs first. In this outcome measure, PFS was based on BICR.

  2. Percentage of Participants Wiht Objective Response (OR) Based on Investigator Assessment [ Time Frame: Randomization up to 65 months ]
    OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on investigator assessment.

  3. Percentage of Participants With Objective Response (OR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline) [ Time Frame: Randomization up to 65 months ]
    OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on investigator assessment.

  4. Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR) [ Time Frame: Randomization up to 65 months ]
    OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on BICR.

  5. Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline) [ Time Frame: Randomization up to 65 months ]
    OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on BICR.

  6. Duration of Response (DOR) Based on Investigator Assessment (Participants With Objective Disease Response) [ Time Frame: Randomization up to 65 months ]
    DOR was defined as the time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. DOR data was censored on the date of the last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, DOR was based on investigator assessment.

  7. Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) (Participants With Objective Disease Response) [ Time Frame: Randomization up to 65 months ]
    DOR was defined as the time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. DOR data was censored on the date of the last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, DOR was based on BICR.

  8. Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment [ Time Frame: Randomization up to 65 months ]
    DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on investigator assessment.

  9. Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline) [ Time Frame: Randomization up to 65 months ]
    DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on investigator assessment.

  10. Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR) [ Time Frame: Randomization up to 65 months ]
    DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on BICR.

  11. Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline) [ Time Frame: Randomization up to 65 months ]
    DC/CBR was defined as CR, PR, or stable disease (SD) >=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis <10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on BICR.

  12. Overall Survival (OS) [ Time Frame: Randomization up to 65 months ]
    OS was defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was assessed using Kaplan-Meier methods.

  13. 1-Year, 2-Year and 3-Year Survival Probability [ Time Frame: Randomization up to 65 months ]
    OS was defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. The 1-year survival probability was estimated using the Kaplan-Meier method and a 2-sided 95% confidence interval (CI) for the log [-log(1 year survival probability)] was be calculated using a normal approximation, and then back transformed to give a CI for the 1-year survival probability itself. The 2-year, and 3-year survival probabilities were estimated similarly.

  14. Number of Participants With Treatment-Emergent Adverse Events (All Causalities) [ Time Frame: Randomization up to 65 months ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Participants were counted only once per treatment in each row.

  15. Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) [ Time Frame: Randomization up to 65 months ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by the investigator (Yes/No). Participants were counted only once per treatment in each row.

  16. Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology [ Time Frame: Randomization up to 65 months ]
    The laboratory results were graded according to the National Cancer Institute (NCI) CTCAE v4.0 severity grade. Shift tables were provided to examine the distribution of laboratory toxicities. The following hematology parameters had met the criteria of CTCAE grade shift change from Grade <=2 at baseline to Grade 3 or 4 post baseline: neutrophils (absolute), white blood cells, platelets, anemia and hemoglobin increased.

  17. Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry [ Time Frame: Randomization up to 65 months ]
    The laboratory results were graded according to the National Cancer Institute (NCI) CTCAE v4.0 severity grade. Shift tables were provided to examine the distribution of laboratory toxicities. The following chemistry parameters had met the criteria of CTCAE grade shift change from Grade <=2 at baseline to Grade 3 or 4 post baseline: alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia.

  18. Trough Plasma Concentration of Palbociclib [ Time Frame: Pre-dose on Day 14 of Cycle 1 and Cycle 2 ]
    Summary of palbociclib trough concentrations

  19. Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores [ Time Frame: Baseline up to Cycle 65 Day 1 ]
    The EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/depression); a participant was asked to rate each state on a 3 level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment.

  20. Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores [ Time Frame: Baseline up to Cycle 65 Day 1 ]
    The EQ VAS recorded the participant's self rated questionnaire to assess generic health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). Published weights were available that allow for the creation of a single summary score.

  21. Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score [ Time Frame: Baseline up to Cycle 65 Day 1 ]
    The Functional Assessment of Cancer Therapy (FACT) is a modular approach to assess participant health related quality of life using a "core" set of questions (FACT-G) as well as a cancer site specific module. The FACT-G was a 27-item compilation of general questions divided into 4 domains: Physical Well Being, Social/Family Well Being, Emotional Well Being, and Functional Well Being. The FACT-B consists of the FACT-G (27 items) and a breast specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a 5-level scale ranging from 0=Not at all to 4=Very much. FACT-B total score = FACT-G + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-148, with 0 being the worst possible score and 148 the best. A positive change of the total score indicated improvement from baseline and a negative change indicated deterioration.

  22. Median Baseline Percent (%) Positive Cells for Ki67 [ Time Frame: Baseline ]
    Archived formalin-fixed paraffin embedded (FFPE) specimen from the original diagnostic tumor tissue was collected and sent to the sponsor-designated central laboratories for assessment of Ki67 associated with sensitivity and/or resistance to Palbociclib.

  23. Number of Participants With Detection in Estrogen Receptor (ER) [ Time Frame: Baseline ]
    Archived formalin-fixed paraffin embedded (FFPE) specimen from the original diagnostic tumor tissue was collected and sent to the sponsor-designated central laboratories for assessment of ER associated with sensitivity and/or resistance to Palbociclib.



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 to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult Asian women with locoregionally recurrent or metastatic disease not amenable to curative therapy
  • Confirmed diagnosis of ER positive breast cancer
  • No prior systemic anti-cancer therapy for advanced ER+ disease
  • Postmenopausal women
  • Measurable disease as per Response Evaluation Criterion in Solid Tumors [RECIST] or bone-only disease
  • Eastern Cooperative Oncology Group [ECOG] 0-1
  • Adequate organ and marrow function
  • Patient must agree to provide tumor tissue

Exclusion Criteria:

  • Confirmed diagnosis of HER2 positive disease
  • Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
  • Known uncontrolled or symptomatic CNS metastases
  • Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment
  • Prior treatment with any CDK 4/6 inhibitor

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): NCT02297438


Locations
Show Show 55 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] July 21, 2014
Statistical Analysis Plan  [PDF] October 14, 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: NCT02297438    
Other Study ID Numbers: A5481027
First Posted: November 21, 2014    Key Record Dates
Results First Posted: November 18, 2021
Last Update Posted: January 31, 2022
Last Verified: January 2022
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
Keywords provided by Pfizer:
breast cancer
postmenopausal women
estrogen-receptor positive
HER2 negative
locoregionally recurrent
metastatic
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Palbociclib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors