Palbociclib In Combination With Letrozole As Treatment Of Post-Menopausal Women With HR+, HER2- Advanced Breast Cancer

A STUDY OF PALBOCICLIB IN COMBINATION WITH LETROZOLE AS TREATMENT OF POST-MENOPAUSAL WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER FOR WHOM LETROZOLE THERAPY IS DEEMED APPROPRIATE

A study of palbociclib in combination with letrozole as treatment of post-menopausal women with hormone receptor-positive, her2-negative advanced breast cancer for whom letrozole therapy is deemed appropriate.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Palbociclib; Drug: Letrozole

Detailed Description

To provide access to palbociclib to post-menopausal patients with hormone receptor-positive [HR(+)], HER2-negative [HER2(-)] ABC who are deemed appropriate for letrozole therapy.

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Benjamin Carl Forster
    • North Sydney, New South Wales, Australia, 2060
      • Dr. Alexander Maxwell Menzies
    • North Sydney, New South Wales, Australia, 2060
      • HPS Pharmacies - North Sydney
    • North Sydney, New South Wales, Australia, 2060
      • Mater Hospital Sydney
    • North Sydney, New South Wales, Australia, 2060
      • Professor Frances Mary Boyle
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital - Clinical Trials Pharmacy
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital, Dept. of Medical Oncology
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Icon Cancer Care Wesley
    • Auchenflower, Queensland, Australia, 4066
      • River City Pharmacy
    • Chermside, Queensland, Australia, 4032
      • Icon Cancer Care Chermside
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Care South Brisbane
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Care, Corporate Office
    • Southport, Queensland, Australia, 4215
      • Icon Cancer Care Southport
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre-Pharmacy Department
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Centre
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre Pharmacy
    • St Albans, Victoria, Australia, 3021
      • Sunshine Hospital
    • St. Albans, Victoria, Australia, 3021
      • Sunshine Hospital Pharmacy
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Murdoch, Western Australia, Australia, 6150
      • Pharmacy Department
• India
  • Delhi
    • New Delhi, Delhi, India, 110 085
      • Rajiv Gandhi Cancer Institute And Research Centre
    • New Delhi, Delhi, India, 110029
      • Dr. B.R.A Institute Rotary Cancer Hospital, All India Institue of Medical Sciences
  • Gujarat
    • Ahmedabad, Gujarat, India, 380016
      • The Gujarat Cancer & Research Institute, M.P Shah Cancer Hospital
  • Karnataka
    • Bangalore, Karnataka, India, 560017
      • Manipal Hospital
    • Bangalore, Karnataka, India, 560027
      • HealthCare Global Enterprises Ltd.
    • Manipal, Karnataka, India, 576104
      • Kasturba Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400 012
      • Tata Memorial Centre, Tata Memorial Hospital
    • Nagpur, Maharashtra, India, 440012
      • Meditrina Institute Of Medical Sciences
    • Nashik, Maharashtra, India, 422005
      • Shatabdi Hospital
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
    • Pune, Maharashtra, India, 411 004
      • Deenanath Mangeshkar Hospital and Research Center
  • Tamilnadu
    • Chennai, Tamilnadu, India, 600 035
      • Apollo Speciality Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Post-menopausal women (>=18 years of age) with proven diagnosis of advanced carcinoma of the breast (ER(+) and/or PgR(+) and HER2(-)) who are appropriate for letrozole therapy (in the first-line advanced/metastatic disease setting).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate bone marrow, liver, and renal function.

Exclusion Criteria:

• Prior treatment with any CDK inhibitor .
• QTc >480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
• High cardiovascular risk, including, but not limited to myocardial infarction, severe/unstable angina, severe cardiac dysrhythmias, and symptomatic pulmonary embolism in the past 6 months of enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental arm; Palbociclib plus Letrozole	Drug: Palbociclib; 125 mg/d capsules orally for 3 out of 4 weeks in repeated cycles; Other Names: IBRANCE; Drug: Letrozole; 2.5 mg/d tablets orally on a continuous regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as treatment emergent adverse events (TEAEs). AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. A serious adverse event (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.	Baseline up to 28 days after last dose of study treatment, an average of 14 months
Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity.	Baseline up to 28 days after last dose of study treatment, an average of 14 months
Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. An 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. Palbociclib-related TEAEs were determined by the investigator.	Baseline up to 28 days after last dose of study treatment, an average of 14 months
Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related)	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. Palbociclib-related TEAEs were determined by the investigator.	Baseline up to 28 days after last dose of study treatment, an average of 14 months
Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related)	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. Palbociclib-related SAEs were determined by the investigator.	Baseline up to 28 days after last dose of study treatment, an average of 14 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Complete Response and Partial Response	Tumor response assessments were evaluated as per local guidelines by investigators and were collected in the CRF. No response confirmation was applied.	Baseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year
The Objective Response Rate (ORR)	The tumor response was based on the response reported by investigator per local practice. No response confirmation was applied. ORR was defined as the percentage of participants with complete response or partial response relative to all as-treated population.	Baseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year
EQ-5D Health Utility Index Score	The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The first part was a 5 item questionnaire designed to assess health status in terms of a single index value or utility score. It consisted of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). A respondent was asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment. The answers given to the 5 descriptors permit to find 243 unique health states which can be converted into a single EQ-5D index value by published algorithms. For the EQ-5D index, published weights are available that allow for the creation of a summary score ranging from -0.594 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health.	The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.
Change From Baseline in EQ-5D Health Utility Index Score	The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The first part was a 5 item questionnaire designed to assess health status in terms of a single index value or utility score. It consisted of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). A respondent was asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment. The answers given to the 5 descriptors permit to find 243 unique health states which can be converted into a single EQ-5D index value by published algorithms. For the EQ-5D index, published weights are available that allow for the creation of a summary score ranging from -0.594 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health.	The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.
EQ-VAS Score	The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The second part consisted of a visual analogue scale (the EuroQol-visual analogue scale [EQ-VAS]). The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state)	The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.
Change From Baseline in EQ-VAS Score	The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The second part consisted of a visual analogue scale (the EuroQol-visual analogue scale [EQ-VAS]). The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state)	The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2016
• Primary Completion (Actual): July 25, 2019
• Study Completion (Actual): July 25, 2019

Study Registration Dates

• First Submitted: January 22, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Hormone receptor positive advanced breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Palbociclib
• Other Study ID Numbers: A5481037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.