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

Breast Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT04274933
• Other study ID #: M19-992
• Secondary ID: 2019-003452-36
• Status: Terminated
• Phase: Phase 1
• Start date: May 21, 2020
• Est. completion date: October 8, 2020

Study information

• Verified date: October 2020
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: October 8, 2020
• Est. primary completion date: October 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cancer
• Disease Progression

Intervention

Drug:
• Venetoclax
Tablet; Oral
• Capecitabine
Tablet; Oral

Locations

Country	Name	City	State
Germany	Charite Universitaetsmedizin Berlin /ID# 215287	Berlin
Germany	Universitaetsklinik Heidelberg /ID# 214679	Heidelberg	Baden-Wuerttemberg
Germany	Universitatsklinikum Tubingen /ID# 217021	Tuebingen
Germany	Universitaetsklinikum Ulm /ID# 214678	Ulm	Thueringen
Japan	Aichi Cancer Center Hospital /ID# 224527	Nagoya-shi	Aichi
Puerto Rico	Pan American Center for Oncology Trials, LLC /ID# 216862	Rio Piedras
Puerto Rico	GCM Medical Group PSC - Hato Rey /ID# 216904	San Juan
United States	Dana-Farber Cancer Institute /ID# 214832	Boston	Massachusetts
United States	Massachusetts General Hospital /ID# 214833	Boston	Massachusetts
United States	Greenville Health System Cance /ID# 216059	Greenville	South Carolina
United States	MD Anderson Cancer Center /ID# 214867	Houston	Texas
United States	Joliet Oncology-Hematology Associates, LTD /ID# 215051	Joliet	Illinois
United States	Masonic Cancer Center /ID# 216101	Minneapolis	Minnesota
United States	Vanderbilt University Med Ctr /ID# 213852	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center /ID# 214886	New York	New York
United States	University of Pennsylvania /ID# 216357	Philadelphia	Pennsylvania
United States	Utah Cancer Specialists /ID# 215375	Salt Lake City	Utah
United States	Swedish Cancer Institute /ID# 216120	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Germany,  Japan,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Dose Limiting Toxicities (DLTs)	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.	Up to 21 days after first dose of study drug
Primary	Maximum observed plasma concentration (Cmax) of venetoclax	Maximum observed plasma concentration (Cmax) of venetoclax	Up to 9 days after first dose of study drug
Primary	Maximum observed plasma concentration (Cmax) of capecitabine	Maximum observed plasma concentration (Cmax) of capecitabine.	Up to 9 days after first dose of study drug
Primary	Maximum observed plasma concentration (Cmax) of 5-fluorouracil	Maximum observed plasma concentration (Cmax) of 5-fluorouracil.	Up to 9 days after first dose of study drug
Primary	Time to Cmax (peak time, Tmax) of venetoclax	Time to Cmax (peak time, Tmax) of venetoclax.	Up to 9 days after first dose of study drug
Primary	Time to Cmax (peak time, Tmax) of 5-fluorouracil	Time to Cmax (peak time, Tmax) of 5-fluorouracil.	Up to 9 days after first dose of study drug
Primary	Time to Cmax (peak time, Tmax) of capecitabine	Time to Cmax (peak time, Tmax) of capecitabine.	Up to 9 days after first dose of study drug
Primary	Area under the plasma concentration versus time curve (AUC) for venetoclax up to 24 hours post-dose (AUC0-24)	Area under the plasma concentration versus time curve for venetoclax up to 24 hours post-dose.	Up to 24 hours
Primary	Area under the plasma concentration versus time curve (AUC) for capecitabine/5-fluorouracil up to 12 hours post-dose (AUC0-12)	Area under the plasma concentration versus time curve for capecitabine/5-fluorouracil up to 12 hours post-dose.	Up to 12 hours

External Links

•   This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.