Ribociclib&Belinostat In Patients w Metastatic Triple Neg Breast Cancer & Recurrent Ovarian Cancer w Response Prediction By Genomics

NCT04315233 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 130492U54CA209978
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Metastatic Breast Cancer; Recurrent Ovarian Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of Dose Limiting Toxicity (DLT)

  This outcome measure will report the count of participants who experienced DLTs during the DLT period. The DLT period is defined as the first cycle of treatment (from cycle one day one dosing to cycle two day 1). Patients will be assessed over this period for the occurrence of adverse events, per CTCAE v5.0. Any of the following events occurring within the defined DLT period which are attributable (possibly, probably, or definitely related) to any or all agents in the combination will be classified as a DLT: * Hematologic: * Grade 3 Thrombocytopenia with clinically significant bleeding * Grade 4-5 Thrombocytopenia * Grade ≥ 3 Febrile Neutropenia * Grade 4-5 Neutropenia lasting \>7 days * Non-Hematologic: * Any grade ≥ 4 toxicity * Any grade 3 toxicity lasting \>48 hours despite maximal medical therapy except for clinically non-significant laboratory abnormalities. * Grade ≥ 3 Electrocardiogram (ECG) corrected QT interval by Fredericia (QTcF) prolongation

  up to 28 days after initiation of study treatment

Secondary Outcomes (3)

• Frequency of Attributed Adverse Events (AEs) and Serious Adverse Events (SAEs)

  up to 5 months from the start of study treatment

• Progression Free Survival (PFS)

  up to 4 months

• Objective Response Rate (ORR)

  up to 4 months

Study Arms (2)

Cohort 1: Dose Escalation Cohort

EXPERIMENTAL

Ribociclib and belinostat will be given at escalating doses and on multiple administration schedules throughout the dose escalation component of the study. The MTD identified in the dose escalation component will be used to define the dose and administration schedule used in the dose expansion.

Drug: Ribociclib; Drug: Belinostat

Cohort 2: Dose expansion cohort

EXPERIMENTAL

Participant will be enrolled in dose expansion cohort at the identified Recommended Phase 2 Dose (RP2D). Dose escalation will be open to the enrollment of patients diagnosed with triple-negative breast cancer or ovarian cancer. However, dose expansion will only be open to the enrollment of patients diagnosed with triple-negative breast cancer

Drug: Ribociclib; Drug: Belinostat

Interventions

Ribociclib DRUG

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

Cohort 1: Dose Escalation Cohort; Cohort 2: Dose expansion cohort

Belinostat DRUG

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.

Cohort 1: Dose Escalation Cohort; Cohort 2: Dose expansion cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Platinum-resistant (defined as progression within 12 months of last platinum therapy administration), pathologically confirmed serous ovarian cancer that is recurrent and is unresectable, in the opinion of the enrolling investigator.
• For dose expansion cohort 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.
• For all patients:

You may not qualify if:

• 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.
• Active infection requiring systemic therapy.
• History of allergy or hypersensitivity to belinostat, ribociclib, or their binders.
• Uncontrolled arrhythmia, congestive heart failure or angina. Patients who have had a myocardial infarction, symptomatic pericarditis, or cardiac surgery should be at least 6 months from the event and free of active symptoms
• Known left ventricular ejection fraction \< 50%. (Echocardiogram is not required for study entry)
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
• Congenital long QT syndrome.
• Baseline QTcF\>450 msec. The heart rate on the qualifying ECG must be between 50 and 90 BPM.
• Concurrent use of medication known to inhibit UGT1A1. Patients currently taking these medications must have discontinued ≥7 days prior to treatment day 1.
• Concurrent use of herbal supplements, unless approved by the prinicipal investigator. Patients currently taking herbal supplements must have discontinued ≥ 7 days prior to treatment day 1.
• Concurrent use of medication with a known risk of inducing Torsades de Pointes (on the known risk list of crediblemeds.org) that cannot be discontinued or switched to a different medication ≥ 7 days prior to starting the study drug.
• Unresolved diarrhea ≥ Grade 2, per CTCAE v5.0.

Sponsors & Collaborators

• University of Utah: lead
• Novartis: collaborator
• Acrotech Biopharma: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms

Interventions

ribociclib; belinostat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: IIT Data Management Team
• Organization: Research Compliance Office, Huntsman Cancer Institute

IITDataManagement@hci.utah.edu

801-213-6215

Study Officials

• Theresa Werner, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: modified 3+3 dose escalation followed by an expansion cohort at the identified Recommended Phase 2 Dose (RP2D). Dose escalation will be open to the enrollment of patients diagnosed with triple-negative breast cancer or ovarian cancer. However, dose expansion will only be open to the enrollment of patients diagnosed with triple-negative breast cancer

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 19, 2020
• Study Start: May 3, 2021
• Primary Completion: March 14, 2024
• Study Completion: September 25, 2025
• Last Updated: September 4, 2026
• Results First Posted: September 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)