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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

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ClinicalTrials.gov Identifier: NCT04274933
Recruitment Status : Terminated (Company Decision)
First Posted : February 18, 2020
Last Update Posted : October 29, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

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
Breast Cancer Cancer Drug: Venetoclax Drug: Capecitabine Phase 1

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Study Type : Interventional  (Clinical Trial)
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 : October 8, 2020
Actual Study Completion Date : October 8, 2020

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Number of participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to 12 hours ]
    Area under the plasma concentration versus time curve for capecitabine/5-fluorouracil up to 12 hours post-dose.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04274933


Locations
Show Show 18 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
Additional Information:
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT04274933    
Other Study ID Numbers: M19-992
2019-003452-36 ( EudraCT Number )
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: October 29, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Breast Neoplasms
Disease Progression
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Disease Attributes
Pathologic Processes
Capecitabine
Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents