Breast Cancer, Cancer
Conditions
Keywords
Breast Cancer, Metastatic, Locally Advanced, Venetoclax, Capecitabine, Hormone Receptor Positive, HER2 Negative
Brief summary
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.
Interventions
DRUGVenetoclax
Tablet; Oral
DRUGCapecitabine
Tablet; Oral
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose Limiting Toxicities (DLTs) | Up to 21 days after first dose of study drug | 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. |
| Maximum observed plasma concentration (Cmax) of venetoclax | Up to 9 days after first dose of study drug | Maximum observed plasma concentration (Cmax) of venetoclax |
| Maximum observed plasma concentration (Cmax) of capecitabine | Up to 9 days after first dose of study drug | Maximum observed plasma concentration (Cmax) of capecitabine. |
| Maximum observed plasma concentration (Cmax) of 5-fluorouracil | Up to 9 days after first dose of study drug | Maximum observed plasma concentration (Cmax) of 5-fluorouracil. |
| Time to Cmax (peak time, Tmax) of venetoclax | Up to 9 days after first dose of study drug | Time to Cmax (peak time, Tmax) of venetoclax. |
| Time to Cmax (peak time, Tmax) of 5-fluorouracil | Up to 9 days after first dose of study drug | Time to Cmax (peak time, Tmax) of 5-fluorouracil. |
| Time to Cmax (peak time, Tmax) of capecitabine | Up to 9 days after first dose of study drug | Time to Cmax (peak time, Tmax) of capecitabine. |
| Area under the plasma concentration versus time curve (AUC) for venetoclax up to 24 hours post-dose (AUC0-24) | Up to 24 hours | Area under the plasma concentration versus time curve for venetoclax up to 24 hours post-dose. |
| Area under the plasma concentration versus time curve (AUC) for capecitabine/5-fluorouracil up to 12 hours post-dose (AUC0-12) | Up to 12 hours | Area under the plasma concentration versus time curve for capecitabine/5-fluorouracil up to 12 hours post-dose. |
Countries
Germany, Japan, Puerto Rico, United States
Outcome results
None listed