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.
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.
Previous use of CDK 4/6 or HDAC inhibitors for cancer treatment
Major surgery, radiotherapy, anticancer therapy, or investigational agents ≤ 4 weeks of treatment day 1 or ≤5 half-lives, whichever is shorter.
Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease unless determined by the treating physician that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
Medical condition that in the opinion of the enrolling investigator would require the use of valproic acid within ≤ 5 days of the first dose of belinostat or while on study.
Single group
Ribociclib
DrugRibociclib 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
Belinostat
DrugBelinostat 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.
MTD of ribociclib and belinostat combination
incidence of DLTs during the defined DLT period
frequency and characterization of AEs and SAEs
safety of ribociclib and belinostat combination
Progression Free Survival (PFS)
assess efficacy
Objective Response Rate (ORR)
assess efficacy
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