RECRUITING

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

Conditions

Metastatic Breast Cancer Recurrent Ovarian Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2021-05-03

Study Completion:2026-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04315233

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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. * Age ≥ 18. * ECOG performance Status ≤ 2. * Able to swallow pills. * Adequate organ function as defined as: * Hematologic: * ANC \> 1,500/mm3 * Platelets \> 100,000/mm3 * Hemoglobin \> 9g/dL * Hepatic: * Serum bilirubin levels ≤1.5 mg/dL. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis. Bilirubin above 1.5mg/dL due to Gilbert's is still excluded. * Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 X upper limit of normal. * AST(SGOT)/ALT(SGPT) ≤ 5 × institutional ULN for patients with liver metastasis. * Alkaline phosphatase \< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis * Renal: * Serum creatinine levels ≤1.5 mg/dL * Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of study medication: * Potassium * Magnesium * Total Calcium (corrected for serum albumin) * Coagulation ---INR ≤1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug) * Presence of ≥ 1 metastatic sites of disease that can be safely accessed for biopsy and patient willingness to undergo fresh tissue biopsies of up to 3 lesions. (Safely accessible means risk of mortality or major morbidity \< 1.5%, such as core needle biopsy of breast, superficial lymph node, subcutaneous nodule, peripheral liver nodule, pleural nodule, omental nodule, etc. or per investigator discretion) * Negative serum or urine pregnancy test at screening for women of childbearing potential. * Agrees to continue use of approved birth control for at least 6 months after receiving the last dose of study drugs. See section 7.3 for list of approved birth control methods. * Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.	* 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. * Use of any of the following substances ≤ 7 days prior to the start of the treatment: * Known strong and moderate inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pomelos, star-fruit, and Seville oranges. * Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. Examples include certain benzodiazepines such as alprazolam and anti-seizure medications such as carbamazepine. Ultimately determination of drugs with a narrow therapeutic window is left to the discretion of the principal investigator. * Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. * Impaired GI function that may alter absorption of medicines, such as uncontrolled inflammatory bowel disease, uncontrolled vomiting, or major stomach or small bowel resection. * Pregnant or breast feeding * Women of child-bearing potential defined as all women physiologically capable of becoming pregnant or men whose female partner is of child-bearing potential, unless they are using highly effective methods of contraception during the study treatment and for 6 months after stopping the treatment. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment * Male partner sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient and the success of the vasectomy must be medically confirmed as per local practice. * Placement of an intrauterine device (IUD). * Use of hormonal contraception plus a barrier contraceptive. * Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. * Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable viral load. * Malignancy other than breast carcinoma or ovarian cancer (dose escalation) anticipated to need systemic treatment within 1 year in the opinion of the enrolling investigator.

Inclusion Criteria

Exclusion Criteria

* 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.
* 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.
* Age ≥ 18.
* ECOG performance Status ≤ 2.
* Able to swallow pills.
* Adequate organ function as defined as:
* Hematologic:
* ANC \> 1,500/mm3
* Platelets \> 100,000/mm3
* Hemoglobin \> 9g/dL
* Hepatic:
* Serum bilirubin levels ≤1.5 mg/dL. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis. Bilirubin above 1.5mg/dL due to Gilbert's is still excluded.
* Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 X upper limit of normal.
* AST(SGOT)/ALT(SGPT) ≤ 5 × institutional ULN for patients with liver metastasis.
* Alkaline phosphatase \< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
* Renal:
* Serum creatinine levels ≤1.5 mg/dL
* Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of study medication:
* Potassium
* Magnesium
* Total Calcium (corrected for serum albumin)
* Coagulation ---INR ≤1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug)
* Presence of ≥ 1 metastatic sites of disease that can be safely accessed for biopsy and patient willingness to undergo fresh tissue biopsies of up to 3 lesions. (Safely accessible means risk of mortality or major morbidity \< 1.5%, such as core needle biopsy of breast, superficial lymph node, subcutaneous nodule, peripheral liver nodule, pleural nodule, omental nodule, etc. or per investigator discretion)
* Negative serum or urine pregnancy test at screening for women of childbearing potential.
* Agrees to continue use of approved birth control for at least 6 months after receiving the last dose of study drugs. See section 7.3 for list of approved birth control methods.
* Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.

* 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.
* Use of any of the following substances ≤ 7 days prior to the start of the treatment:
* Known strong and moderate inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pomelos, star-fruit, and Seville oranges.
* Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. Examples include certain benzodiazepines such as alprazolam and anti-seizure medications such as carbamazepine. Ultimately determination of drugs with a narrow therapeutic window is left to the discretion of the principal investigator.
* Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise.
* Impaired GI function that may alter absorption of medicines, such as uncontrolled inflammatory bowel disease, uncontrolled vomiting, or major stomach or small bowel resection.
* Pregnant or breast feeding
* Women of child-bearing potential defined as all women physiologically capable of becoming pregnant or men whose female partner is of child-bearing potential, unless they are using highly effective methods of contraception during the study treatment and for 6 months after stopping the treatment. Highly effective contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male partner sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient and the success of the vasectomy must be medically confirmed as per local practice.
* Placement of an intrauterine device (IUD).
* Use of hormonal contraception plus a barrier contraceptive.
* Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
* Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable viral load.
* Malignancy other than breast carcinoma or ovarian cancer (dose escalation) anticipated to need systemic treatment within 1 year in the opinion of the enrolling investigator.

Contacts and Locations

Study Contact

Janna Espinosa

CONTACT

801-585-0571

janna.espinosa@hci.utah.edu

Principal Investigator

Theresa Werner, MD

PRINCIPAL_INVESTIGATOR

Huntsman Cancer Institute

Study Locations (Sites)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112

United States

Inova Schar Cancer Institute

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: University of Utah

Theresa Werner, MD, PRINCIPAL_INVESTIGATOR, Huntsman Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-05-03

Study Completion Date2026-08

Study Record Updates

Study Start Date2021-05-03

Study Completion Date2026-08

Terms related to this study

Additional Relevant MeSH Terms

Metastatic Breast Cancer
Recurrent Ovarian Carcinoma