Palbociclib, Letrozole & Venetoclax in ER and BCL-2 Positive Breast Cancer (PALVEN)
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|ClinicalTrials.gov Identifier: NCT03900884|
Recruitment Status : Not yet recruiting
First Posted : April 3, 2019
Last Update Posted : September 11, 2019
This study is investigating the combination of palbociclib, letrozole and venetoclax in ER and BCL-2 positive locally advanced or metastatic breast cancer.
It is hypothesised that venetoclax may augment the actions of palbociclib and letrozole in these patient groups. The primary objective of the study is to determine the maximum tolerated dose of the combination treatment, which can be used in subsequent studies. The study will also investigate disease response and survival.
Participants will receive palbociclib (daily, on days 1-21 of each 28 day cycle), letrozole (daily, on days 1-28 of each 28 day cycle) and venetoclax (daily, on days 1-21 of each 28 day cycle) until the last patient has completed 18 months treatment on the study.
|Condition or disease||Intervention/treatment||Phase|
|Breast Neoplasm Female||Drug: Venetoclax Drug: Palbociclib Drug: Letrozole||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a Phase 1b, open-label, multicentre dose escalation study of venetoclax in combination with palbociclib and letrozole in patients with ER positive and BCL-2 positive metastatic breast cancer. The study will enrol up to 36 patients with metastatic breast cancer, with the objective of defining the MTD of venetoclax in combination with palbociclib and letrozole. There will be up to a total of 6 dose levels. Three 'step-down' levels will also be included to incorporate the options of reducing the dose of palbociclib if required. The MTD will be the RP2D of palbociclib, letrozole and venetoclax.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Study of Palbociclib, Letrozole and Venetoclax in ER and BCL-2 Positive Locally Advanced or Metastatic Breast Cancer|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||March 2023|
Experimental: Letrozole + Palbociclib + Venetoclax
The Letrozole dose is 2.5 mg (D1-28) for all dose levels.
Starting dose Level 1: Palbociclib 100 mg (D1-21) and Venetoclax 100 mg (D1-21) daily.
At commencement of study: Venetoclax will commence at 100 mg daily (oral) for days 1-21 of each 28 day cycle. This is a dose finding study so doses will be adjusted between 100 and 800 mg/day depending on dose escalation results and recommendation of the safety committee.
At commencement of study: Palbociclib will commence at 100 mg daily (oral) for days 1-21 of each 28 day cycle. This is a dose finding study so doses will be adjusted between 75 and 125 mg/day depending on dose escalation results and recommendation of the safety committee.
Letrozole will be dosed daily at a fixed dose of 2.5 mg/day throughout the study.
- Determination of the Maximum Tolerated Dose (MTD), dose-limiting toxicities (DLTs) and recommended phase 2 dose of drug combination of palbociclib, letrozole and venetoclax. [ Time Frame: 36 months ]To determine the MTD and DLTs of the combination of palbociclib, letrozole and venetoclax in ER positive, BCL-2 positive, HER2 negative metastatic breast cancer or locally advanced breast cancer not amenable to surgical or local therapy with curative intent, and to identify the recommended Phase 2 dose.
- Safety profile of the combination of palbociclib, letrozole and venetoclax: CTCAE V 5 [ Time Frame: maximum 36 months ]Toxicities measured using CTCAE V 5
- Response Rate [ Time Frame: 24 weeks ]To describe the best response (according to RECIST v1.1), defined as Complete Response (CR) or Partial Response (PR) or stable disease (SD) at 24 weeks.
- Overall survival [ Time Frame: 36 months ]Overall survival (OS) defined as the time from commencement of the study to date of death from any cause
- Clinical benefit rate [ Time Frame: 36 months ]To estimate clinical benefit rate (CBR), defined as CR, PR or SD.
- Patient reported outcomes [ Time Frame: 36 months ]Defined as treatment-related symptoms, patient functioning, and health-related quality of life associated with venetoclax in combination with palbociclib and letrozole. Assessed through patient reported outcomes using a validated quality of life questionnaire - EORTC QLQ C30. The questionnaire is deigned to evaluate change in quality of life over time. Outcomes are rated by the patient on a numerical scale over 28 questions of between 1-4 With 1 being no issue to 4 being a significant issue. There are an additional 2 questions regarding overall quality of life which are rated on a numerical scale 1-7 with 1 being the poorest and 7 being excellent.
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): NCT03900884
|Contact: Geoffrey Lindeman, MBBS FRACP||+61393452805||Geoffrey.Lindeman@petermac.org|
|Contact: Kirsten Hoggemail@example.com|
|Peter MacCallum Cancer Centre|
|Melbourne, Victoria, Australia, 3000|
|Contact: Geoffrey Lindeman, MBBS firstname.lastname@example.org|
|Royal Melbourne Hospital|
|Melbourne, Victoria, Australia, 3052|
|Contact: Geoffrey Lindeman, MBBS email@example.com|
|Melbourne, Victoria, Australia, 3084|
|Contact: Belinda Yeo, MBBS|
|Principal Investigator:||Geoffrey Lindeman||Peter MacCallum Cancer Centre, Australia|