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

NCT04274933 | Terminated Phase 1 FDA Drug

• 2 other identifiers: M19-9922019-003452-36
• Study Type: interventional
• Target: 4
• Locations: 4 countries
• Sites: 18

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.

Conditions

Breast Cancer; Cancer

Keywords

Breast Cancer; Metastatic; Locally Advanced; Venetoclax; Capecitabine; Hormone Receptor Positive; HER2 Negative

Outcome Measures

Primary Outcomes (9)

• 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

• Maximum observed plasma concentration (Cmax) of venetoclax

  Maximum observed plasma concentration (Cmax) of venetoclax

  Up to 9 days after first dose of study drug

• Maximum observed plasma concentration (Cmax) of capecitabine

  Maximum observed plasma concentration (Cmax) of capecitabine.

  Up to 9 days after first dose of study drug

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Dose Escalation: Venetoclax and Capecitabine

EXPERIMENTAL

Venetoclax at various doses will be administered in combination with capecitabine until a recommended dose is determined.

Drug: Venetoclax; Drug: Capecitabine

Dose Expansion: Venetoclax and Capecitabine

EXPERIMENTAL

Venetoclax at the dose identified in Dose Escalation administered in combination with capecitabine.

Drug: Venetoclax; Drug: Capecitabine

Interventions

Venetoclax DRUG

Tablet; Oral

Also known as: Venclexta, ABT-199

Dose Escalation: Venetoclax and Capecitabine; Dose Expansion: Venetoclax and Capecitabine

Capecitabine DRUG

Tablet; Oral

Dose Escalation: Venetoclax and Capecitabine; Dose Expansion: Venetoclax and Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (18)

Joliet Oncology-Hematology Associates, LTD /ID# 215051

Joliet, Illinois, 60435, United States

Location

Massachusetts General Hospital /ID# 214833

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute /ID# 214832

Boston, Massachusetts, 02215, United States

Location

Masonic Cancer Center /ID# 216101

Minneapolis, Minnesota, 55455, United States

Location

Memorial Sloan Kettering Cancer Center /ID# 214886

New York, New York, 10065-6007, United States

Location

University of Pennsylvania /ID# 216357

Philadelphia, Pennsylvania, 19104-5502, United States

Location

Greenville Health System Cance /ID# 216059

Greenville, South Carolina, 29605, United States

Location

Vanderbilt University Med Ctr /ID# 213852

Nashville, Tennessee, 37232-6307, United States

Location

MD Anderson Cancer Center /ID# 214867

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists /ID# 215375

Salt Lake City, Utah, 84106, United States

Location

Swedish Cancer Institute /ID# 216120

Seattle, Washington, 98104, United States

Location

Universitaetsklinik Heidelberg /ID# 214679

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsklinikum Ulm /ID# 214678

Ulm, Thuringia, 89081, Germany

Location

Charite Universitaetsmedizin Berlin /ID# 215287

Berlin, 10117, Germany

Location

Universitatsklinikum Tubingen /ID# 217021

Tübingen, 72076, Germany

Location

Aichi Cancer Center Hospital /ID# 224527

Nagoya, Aichi-ken, 464-8681, Japan

Location

Pan American Center for Oncology Trials, LLC /ID# 216862

Rio Piedras, 00935, Puerto Rico

Location

GCM Medical Group PSC - Hato Rey /ID# 216904

San Juan, 00917-3104, Puerto Rico

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

venetoclax; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: February 18, 2020
• Study Start: May 21, 2020
• Primary Completion: October 8, 2020
• Study Completion: October 8, 2020
• Last Updated: October 29, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); JP (1); PR (2); US (11)