Clinical trial NCT04274933: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Cancer
Keywords: Breast Cancer
Metastatic
Locally Advanced
Venetoclax
Capecitabine
Hormone Receptor Positive
HER2 Negative
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-02-18
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 21 days after first dose of study drug
measure: Maximum observed plasma concentration (Cmax) of venetoclax
timeFrame: Up to 9 days after first dose of study drug
measure: Maximum observed plasma concentration (Cmax) of capecitabine
timeFrame: Up to 9 days after first dose of study drug
measure: Maximum observed plasma concentration (Cmax) of 5-fluorouracil
timeFrame: Up to 9 days after first dose of study drug
measure: Time to Cmax (peak time, Tmax) of venetoclax
timeFrame: Up to 9 days after first dose of study drug
measure: Time to Cmax (peak time, Tmax) of 5-fluorouracil
timeFrame: Up to 9 days after first dose of study drug
measure: Time to Cmax (peak time, Tmax) of capecitabine
timeFrame: Up to 9 days after first dose of study drug
measure: Area under the plasma concentration versus time curve (AUC) for venetoclax up to 24 hours post-dose (AUC0-24)
timeFrame: Up to 24 hours
measure: Area under the plasma concentration versus time curve (AUC) for capecitabine/5-fluorouracil up to 12 hours post-dose (AUC0-12)
timeFrame: Up to 12 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, LTD /ID# 215051
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 214833
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 214832
state: Massachusetts
city: Minneapolis
country: United States
facility: Masonic Cancer Center /ID# 216101
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center /ID# 214886
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 216357
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System Cance /ID# 216059
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Med Ctr /ID# 213852
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center /ID# 214867
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists /ID# 215375
state: Utah
city: Seattle
country: United States
facility: Swedish Cancer Institute /ID# 216120
state: Washington
city: Heidelberg
country: Germany
facility: Universitaetsklinik Heidelberg /ID# 214679
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm /ID# 214678
state: Thueringen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin /ID# 215287
city: Tuebingen
country: Germany
facility: Universitatsklinikum Tubingen /ID# 217021
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital /ID# 224527
state: Aichi
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC /ID# 216862
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC - Hato Rey /ID# 216904
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: