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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

Sponsor
AbbVie (Industry)
Overall Status
Terminated
CT.gov ID
NCT04274933
Collaborator
(none)
4
Enrollment
18
Locations
2
Arms
4.6
Actual Duration (Months)
0.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
4 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 21, 2020
Actual Primary Completion Date :
Oct 8, 2020
Actual Study Completion Date :
Oct 8, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation: Venetoclax and Capecitabine

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

Drug: Venetoclax
Tablet; Oral
Other Names:
  • Venclexta
  • ABT-199

    • Drug: Capecitabine
    Tablet; Oral
    Experimental: Dose Expansion: Venetoclax and Capecitabine

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

    Drug: Venetoclax
    Tablet; Oral
    Other Names:
  • Venclexta
  • ABT-199

    • Drug: Capecitabine
    Tablet; Oral

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. Maximum observed plasma concentration (Cmax) of venetoclax [Up to 9 days after first dose of study drug]

      Maximum observed plasma concentration (Cmax) of venetoclax

    3. Maximum observed plasma concentration (Cmax) of capecitabine [Up to 9 days after first dose of study drug]

      Maximum observed plasma concentration (Cmax) of capecitabine.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Joliet Oncology-Hematology Associates, LTD /ID# 215051 Joliet Illinois United States 60435
    2 Massachusetts General Hospital /ID# 214833 Boston Massachusetts United States 02114
    3 Dana-Farber Cancer Institute /ID# 214832 Boston Massachusetts United States 02215
    4 Masonic Cancer Center /ID# 216101 Minneapolis Minnesota United States 55455
    5 Memorial Sloan Kettering Cancer Center /ID# 214886 New York New York United States 10065-6007
    6 University of Pennsylvania /ID# 216357 Philadelphia Pennsylvania United States 19104-5502
    7 Greenville Health System Cance /ID# 216059 Greenville South Carolina United States 29605
    8 Vanderbilt University Med Ctr /ID# 213852 Nashville Tennessee United States 37232-6307
    9 MD Anderson Cancer Center /ID# 214867 Houston Texas United States 77030
    10 Utah Cancer Specialists /ID# 215375 Salt Lake City Utah United States 84106
    11 Swedish Cancer Institute /ID# 216120 Seattle Washington United States 98104
    12 Universitaetsklinik Heidelberg /ID# 214679 Heidelberg Baden-Wuerttemberg Germany 69120
    13 Universitaetsklinikum Ulm /ID# 214678 Ulm Thueringen Germany 89081
    14 Charite Universitaetsmedizin Berlin /ID# 215287 Berlin Germany 10117
    15 Universitatsklinikum Tubingen /ID# 217021 Tuebingen Germany 72076
    16 Aichi Cancer Center Hospital /ID# 224527 Nagoya-shi Aichi Japan 464-8681
    17 Pan American Center for Oncology Trials, LLC /ID# 216862 Rio Piedras Puerto Rico 00935
    18 GCM Medical Group PSC - Hato Rey /ID# 216904 San Juan Puerto Rico 00917-3104

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT04274933
    Other Study ID Numbers:
    • M19-992
    • 2019-003452-36
    First Posted:
    Feb 18, 2020
    Last Update Posted:
    Oct 29, 2020
    Last Verified:
    Oct 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by AbbVie
    Breast Cancer
    Metastatic
    Locally Advanced
    Venetoclax
    Capecitabine
    Hormone Receptor Positive
    HER2 Negative
    Additional relevant MeSH terms:
    Breast Neoplasms
    Disease Progression
    Capecitabine
    Venetoclax

    Study Results

    No Results Posted as of Oct 29, 2020