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

Study Overview
=================
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.

Official Title
-----------------
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

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Palbociclib
* Drug: Letrozole


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

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

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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hormone receptor positive advanced breast cancer