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

Phase 4
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT02679755
Lead Sponsor
Pfizer
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
252
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 & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Experimental armPalbociclibPalbociclib plus Letrozole
Experimental armLetrozolePalbociclib plus Letrozole
Primary Outcome Measures
NameTimeMethod
Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities)Baseline up to 28 days after last dose of study treatment, an average of 14 months

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.

Number of Participants With Treatment-Emergent Adverse Events (All Causalities)Baseline up to 28 days after last dose of study treatment, an average of 14 months

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.

Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related)Baseline up to 28 days after last dose of study treatment, an average of 14 months

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.

Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related)Baseline up to 28 days after last dose of study treatment, an average of 14 months

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.

Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related)Baseline up to 28 days after last dose of study treatment, an average of 14 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. Palbociclib-related SAEs were determined by the investigator.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Complete Response and Partial ResponseBaseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year

Tumor response assessments were evaluated as per local guidelines by investigators and were collected in the CRF. No response confirmation was applied.

EQ-VAS ScoreThe 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.

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)

EQ-5D Health Utility Index ScoreThe 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.

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 Objective Response Rate (ORR)Baseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year

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.

Change From Baseline in EQ-5D Health Utility Index ScoreThe 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.

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.

Change From Baseline in EQ-VAS ScoreThe 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.

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)

Trial Locations

Locations (34)

HealthCare Global Enterprises Ltd.

🇮🇳

Bangalore, Karnataka, India

Tata Memorial Centre, Tata Memorial Hospital

🇮🇳

Mumbai, Maharashtra, India

Shatabdi Hospital

🇮🇳

Nashik, Maharashtra, India

Deenanath Mangeshkar Hospital and Research Center

🇮🇳

Pune, Maharashtra, India

Sahyadri Super Speciality Hospital

🇮🇳

Pune, Maharashtra, India

Apollo Speciality Hospital

🇮🇳

Chennai, Tamilnadu, India

River City Pharmacy

🇦🇺

Auchenflower, Queensland, Australia

Monash Health

🇦🇺

Clayton, Victoria, Australia

Icon Cancer Care Chermside

🇦🇺

Chermside, Queensland, Australia

Manipal Hospital

🇮🇳

Bangalore, Karnataka, India

Icon Cancer Care, Corporate Office

🇦🇺

South Brisbane, Queensland, Australia

Icon Cancer Care South Brisbane

🇦🇺

South Brisbane, Queensland, Australia

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Flinders Medical Centre-Pharmacy Department

🇦🇺

Bedford Park, South Australia, Australia

Kasturba Hospital

🇮🇳

Manipal, Karnataka, India

Meditrina Institute Of Medical Sciences

🇮🇳

Nagpur, Maharashtra, India

Rajiv Gandhi Cancer Institute And Research Centre

🇮🇳

New Delhi, Delhi, India

Dr. B.R.A Institute Rotary Cancer Hospital, All India Institue of Medical Sciences

🇮🇳

New Delhi, Delhi, India

Professor Frances Mary Boyle

🇦🇺

North Sydney, New South Wales, Australia

Dr. Alexander Maxwell Menzies

🇦🇺

North Sydney, New South Wales, Australia

Royal North Shore Hospital, Dept. of Medical Oncology

🇦🇺

St Leonards, New South Wales, Australia

Icon Cancer Care Southport

🇦🇺

Southport, Queensland, Australia

Sunshine Hospital Pharmacy

🇦🇺

St. Albans, Victoria, Australia

Pharmacy Department

🇦🇺

Murdoch, Western Australia, Australia

Sunshine Hospital

🇦🇺

St Albans, Victoria, Australia

Peter MacCallum Cancer Centre Pharmacy

🇦🇺

Melbourne, Victoria, Australia

Fiona Stanley Hospital

🇦🇺

Murdoch, Western Australia, Australia

The Gujarat Cancer & Research Institute, M.P Shah Cancer Hospital

🇮🇳

Ahmedabad, Gujarat, India

Mater Hospital Sydney

🇦🇺

North Sydney, New South Wales, Australia

Benjamin Carl Forster

🇦🇺

North Sydney, New South Wales, Australia

HPS Pharmacies - North Sydney

🇦🇺

North Sydney, New South Wales, Australia

Royal North Shore Hospital - Clinical Trials Pharmacy

🇦🇺

St Leonards, New South Wales, Australia

Icon Cancer Care Wesley

🇦🇺

Auchenflower, Queensland, Australia

Flinders Medical Centre

🇦🇺

Bedford Park, South Australia, Australia

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