ABBY: ABemacicliB or Abemaciclib and HydroxYchloroquine to Target Minimal Residual Disease in Breast Cancer

Sponsor
Abramson Cancer Center of the University of Pennsylvania (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04523857
Collaborator
(none)
66
Enrollment
1
Location
2
Arms
85.5
Anticipated Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase II randomized, controlled, open label breast cancer clinical trial. 66 patients will be enrolled. The drugs being studied are hydroxychloroquine (Plaquenil) and abemaciclib (also Verzenio). This research study is testing whether using these drugs to target the disseminated tumor cells in bone marrow can reduce their number or eliminate them. Both hydroxychloroquine and abemaciclib are pills that will be taken twice daily. Both are approved by the FDA

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
66 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Pilot Trial of ABemacicliB or Abemaciclib and HydroxYchloroquine to Target Minimal Residual Disease in Breast Cancer Patients ("ABBY")
Anticipated Study Start Date :
Oct 18, 2021
Anticipated Primary Completion Date :
Dec 1, 2027
Anticipated Study Completion Date :
Dec 1, 2028

Arms and Interventions

ArmIntervention/Treatment
Experimental: A (Abema)

Abemaciclib (150 mg BID)

Drug: Abemaciclib
Oral CDK4/6 inhibitor to target bone marrow disseminated tumor cells (DTCs)
Other Names:
  • Verzenio
  • Experimental: B (Abema + HCQ)

    Abemaciclib (100 mg or 150 mg BID*) + Hydroxychloroquine (600 mg BID) *Abemaciclib dose will be determined by safety cohort

    Drug: Abemaciclib
    Oral CDK4/6 inhibitor to target bone marrow disseminated tumor cells (DTCs)
    Other Names:
  • Verzenio
  • Drug: Hydroxychloroquine
    Oral autophagy inhibitor to target bone marrow disseminated tumor cells (DTCs)
    Other Names:
  • Plaquenil
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of treatment-emergent adverse events during cycle 1 of the safety cohort (safety of combination HCQ + Abema) [Toxicity is assessed over the first cycle (4 weeks) of treatment]

      Rate of protocol defined "severe toxicity" during cycle 1 (4 weeks) of combination HCQ 600mg BID and Abema (at 100 mg and 150 mg BID) in a safety cohort of 6 patients at each dose of Abema

    2. Change in bone marrow DTC number evaluated by DTC-IHC assay after 6 cycles of therapy compared to baseline (Efficacy of Abema +/- HCQ in eliminating bone marrow DTCs) [6 cycles (approximately 6 months)]

      Frequency of "clearance" of bone marrow DTCs by arm after 6 cycles of study treatment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically-confirmed, primary, invasive breast cancer diagnosed within 5 years of entry into a companion DTC screening protocol.

    • Qualifying risk status, at diagnosis utilizing receptor testing by ASCO/CAP guidelines

    • Patients must have completed all primary therapy for the index malignancy at least 4 weeks prior to study entry. Prior treatment-related toxicity must be resolved or improving to Grade 1 with the exception of alopecia and up to Grade 3 peripheral neuropathy, prior to study enrollment. Concurrent receipt of adjuvant endocrine and bone modifying agents is allowed per standard of care guidelines. Tamoxifen is not allowed due to drug-drug interactions with HCQ.

    • Bone marrow aspirate after completion of therapy demonstrates detectable DTCs (via IHC)

    • No evidence of recurrent local or distant breast cancer by physical examination, blood tests or symptom-directed imaging, per NCCN guidelines.

    • ECOG performance status =/< 2

    • Ability to swallow oral medications

    • No contraindications to the study medications or uncontrolled medical illness.

    • Adequate bone marrow function

    • Adequate liver function

    • Adequate renal function

    • Anticoagulation is allowed if target INR =/< 1.5 on a stable dose of warfarin or on a stable dose of anticoagulant for >2 weeks at time of randomization

    • Ability to provide informed consent

    Exclusion Criteria

    • Concurrent enrollment on another investigational therapy

    • Prior treatment with a CDK 4/6 inhibitor

    • Known hypersensitivity to hydroxychloroquine or any of its derivatives

    • Patients with hormone-receptor positive breast cancer may not be receiving tamoxifen due to drug-drug interactions with hydroxychloroquine

    • Patients who have received bone modifying agents within 3 months

    • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

    • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.

    • Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of Abema

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Abramson Cancer Center of the University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104

    Sponsors and Collaborators

    • Abramson Cancer Center of the University of Pennsylvania

    Investigators

    • Principal Investigator: Amy Clark, MD, Abramson Cancer Center of the University of Pennsylvania

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Abramson Cancer Center of the University of Pennsylvania
    ClinicalTrials.gov Identifier:
    NCT04523857
    Other Study ID Numbers:
    • UPCC 10119
    First Posted:
    Aug 24, 2020
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Oct 1, 2021
    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.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021