A Phase I/Ib Trial of the CDK4/6 Antagonist Ribociclib And The HDAC Inhibitor Belinostat In Patients With Metastatic Triple Negative Breast Cancer And Recurrent Ovarian Cancer With Response Prediction By Genomics (CHARGE)
University of Utah
Summary
This is an open-label, multi-center, phase I study designed to assess the maximum tolerated dose of ribociclib and belinostat in combination. The trial will open with a dose escalation followed by an expansion cohort at the identified dose. Dose escalation will be open to the enrollment of patients diagnosed with triple-negative breast cancer or ovarian cancer. Dose expansion will only be open to patients diagnosed with triple-negative breast cancer.
Description
We hypothesize that ribociclib plus belinostat will be a well-tolerated and demonstrate activity in women with metastatic triple-negative breast or recurrent ovarian cancers. This trial combines two targeted agents, a CDK inhibitor and a lysine deacetylase (DAC) inhibitor for use as the first targeted treatment for metastatic triple-negative breast cancer. This in itself would be a leap forward for women who currently endure sequential treatment with cytotoxic chemotherapies. However, we will also be using samples from this trial in NIH-funded research on clonal evolution and geographic heter…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: For dose escalation cohorts only: \- Pathologically confirmed breast cancer with the following features: * Measurable disease by RECIST 1.1; * ER and PR ≤ 1% by immunohistochemistry; * Her-2/neu negative (0 or 1+ by immunohistochemistry OR not-amplified by CAP/ASCO standards); * Metastatic or unresectable and locally advanced and not amenable to treatment with curative intent, in the opinion of the enrolling investigator. OR --Pathologically confirmed serous ovarian cancer that is recurrent and is unresectable, in the opinion of the enrolling investigator. For dose exp…
Interventions
- DrugRibociclib
Ribociclib Dose Level 0 (starting dose) 200mg QD Dose Level 1A 400mg QD on Days 8-28 Dose Level 1B 200mg QD Dose Level 2 400mg QD on Days 8-28
- DrugBelinostat
Belinostat Dose Level 0 (starting dose) 600mg/m2 daily for 5 days Dose Level 1A 600mg/m2 daily for 5 days Dose Level 1B 1000mg/m2 daily for 5 days Dose Level 2 1000mg/m2 daily for 5 days \*Administration on 5 consecutive days is preferred. Administration within 7 days allowed as needed to accommodate holidays and infusion schedules.
Locations (2)
- Huntsman Cancer InstituteSalt Lake City, Utah
- Inova Schar Cancer InstituteFairfax, Virginia