Description:
Endocrine therapy is the initial treatment for most hormone receptor positive (HR+), human
epidermal growth factor receptor 2 negative (HER2-) breast cancers. This study will evaluate
the use of venetoclax in combination with capecitabine in adult participants with HR+, HER2-,
metastatic breast cancer (MBC) who had disease progression following treatment that included
a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
Venetoclax is an investigational drug being developed for the treatment of breast cancer.
This study is open-label meaning both the participants and study doctors will know what
treatment is being given. The study includes two phases: dose escalation and dose expansion.
In dose escalation, participants will receive various doses of venetoclax in combination with
capecitabine. In dose expansion, participants will receive the recommended dose of venetoclax
determined during dose escalation in combination with capecitabine. Adult participants with
locally advanced or MBC that is not amenable to curative therapy will be enrolled. Around 42
participants will be enrolled at approximately 20 sites worldwide.
Venetoclax and capecitabine will be administered on a 21-day cycle. During dose escalation,
participants will take various doses of venetoclax as a tablet by mouth once a day and
capecitabine as a tablet by mouth twice per day on days 1 - 14 of each cycle for
approximately 30 weeks. During dose expansion, participants will take venetoclax at the dose
identified during dose escalation as a tablet by mouth once a day and capecitabine as a
tablet by mouth twice per day on days 1 - 14 of each cycle for approximately 30 weeks.
There may be a higher burden for participants in this trial compared to standard of care.
Participants will attend weekly visits during the course of the study at a hospital or
clinic. The effect of the treatment will be checked by medical assessments, blood tests, and
evaluating for side effects.
Title
- Brief Title: A Study to Evaluate the Safety and Tolerability of Venetoclax Tablets in Combination With Capecitabine Tablets in Adult Participants With Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer Who Had Disease Progression During or After CDK4/6 Inhibitor Therapy
- Official Title: A Phase 1b Study of Venetoclax and Capecitabine In Subjects With Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer Who Experienced Disease Progression During or After CDK4/6 Inhibitor Therapy
Clinical Trial IDs
- ORG STUDY ID:
M19-992
- SECONDARY ID:
2019-003452-36
- NCT ID:
NCT04274933
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Venetoclax | Venclexta, ABT-199 | Dose Escalation: Venetoclax and Capecitabine |
| Capecitabine | | Dose Escalation: Venetoclax and Capecitabine |
Purpose
Endocrine therapy is the initial treatment for most hormone receptor positive (HR+), human
epidermal growth factor receptor 2 negative (HER2-) breast cancers. This study will evaluate
the use of venetoclax in combination with capecitabine in adult participants with HR+, HER2-,
metastatic breast cancer (MBC) who had disease progression following treatment that included
a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
Venetoclax is an investigational drug being developed for the treatment of breast cancer.
This study is open-label meaning both the participants and study doctors will know what
treatment is being given. The study includes two phases: dose escalation and dose expansion.
In dose escalation, participants will receive various doses of venetoclax in combination with
capecitabine. In dose expansion, participants will receive the recommended dose of venetoclax
determined during dose escalation in combination with capecitabine. Adult participants with
locally advanced or MBC that is not amenable to curative therapy will be enrolled. Around 42
participants will be enrolled at approximately 20 sites worldwide.
Venetoclax and capecitabine will be administered on a 21-day cycle. During dose escalation,
participants will take various doses of venetoclax as a tablet by mouth once a day and
capecitabine as a tablet by mouth twice per day on days 1 - 14 of each cycle for
approximately 30 weeks. During dose expansion, participants will take venetoclax at the dose
identified during dose escalation as a tablet by mouth once a day and capecitabine as a
tablet by mouth twice per day on days 1 - 14 of each cycle for approximately 30 weeks.
There may be a higher burden for participants in this trial compared to standard of care.
Participants will attend weekly visits during the course of the study at a hospital or
clinic. The effect of the treatment will be checked by medical assessments, blood tests, and
evaluating for side effects.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Dose Escalation: Venetoclax and Capecitabine | Experimental | Venetoclax at various doses will be administered in combination with capecitabine until a recommended dose is determined. | |
| Dose Expansion: Venetoclax and Capecitabine | Experimental | Venetoclax at the dose identified in Dose Escalation administered in combination with capecitabine. | |
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of advanced or metastatic breast cancer that is hormone receptor positive
(HR+) and HER2 negative (HER2-).
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
- Willing to provide tissue biopsy sample prior to start of study treatment, and in
participants with measurable disease, at Day 1 of Cycle 3.
- Escalation cohort: Able to provide a tissue sample obtained at any time in
disease history prior to start of study treatment.
- Expansion cohort: Able to provide a fresh tissue sample from either primary tumor
or metastatic site; if fresh sample collection is deemed unsafe by the
investigator, then an archival tissue block is acceptable if obtained at time of
most recent progression and within 16 weeks of study treatment.
- Experienced disease progression during or after CDK4/6 inhibitor therapy administered
in combination with endocrine therapy for a minimum of 8 weeks prior to progression.
Exclusion Criteria:
- History of receiving systemic cytotoxic chemotherapy in the locally advanced or
metastatic setting.
- Received anti-cancer therapy within the previous 21 days prior to the start of study
drugs.
- No known uncontrolled metastases to the central nervous system (CNS). Participants
with brain metastases are eligible provided they have shown positive clinical and
radiographic stable disease for at least 4 weeks after definitive therapy and have not
used steroids for at least 2 weeks prior to first dose of study drugs.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of participants with Dose Limiting Toxicities (DLTs) |
| Time Frame: | Up to 21 days after first dose of study drug |
| Safety Issue: | |
| Description: | Adverse events that are considered by the investigator to have a reasonable possibility of relationship to the administration of venetoclax in combination with capecitabine will be considered a DLT. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | AbbVie |
Trial Keywords
- Breast Cancer
- Metastatic
- Locally Advanced
- Venetoclax
- Capecitabine
- Hormone Receptor Positive
- HER2 Negative
Last Updated
October 29, 2020
