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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

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 will 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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • Breast Cancer
  • Cancer

Interventions

DrugSynonymsArms
VenetoclaxVenclexta, ABT-199Dose Escalation: Venetoclax and Capecitabine
CapecitabineDose 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 will 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

NameTypeDescriptionInterventions
Dose Escalation: Venetoclax and CapecitabineExperimentalVenetoclax at various doses will be administered in combination with capecitabine until a recommended dose is determined.
  • Venetoclax
  • Capecitabine
Dose Expansion: Venetoclax and CapecitabineExperimentalVenetoclax at the dose identified in Dose Escalation administered in combination with capecitabine.
  • Venetoclax
  • 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 of 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
             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:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

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

Last Updated

February 17, 2020