Metastatic Breast CancerPhase 1CHARGENCT04315233
Ribociclib&Belinostat In Patients w Metastatic Triple Neg Breast Cancer & Recurrent Ovarian Cancer w Response Prediction By Genomics
A Phase 1 study testing Ribociclib and Belinostat in people with Metastatic Breast Cancer and Recurrent Ovarian Carcinoma, run by University of Utah at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer, Recurrent Ovarian Carcinoma
- What is being tested?
- Ribociclib and Belinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 May 2021to 25 Sep 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 40Show fewer
- 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:
- 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.
- Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
Who cannot join
- 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.
Show all 33Show fewer
- 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.
- --Note: Therapy with heparin, low molecular weight heparin (LMWH), an oral factor Xa inhibitor, an oral direct thrombin inhibitor, or fondaparinux is allowed.
- 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.
- --Note: Patients on effective anti-retroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
- Known chronic hepatitis B virus (HBV) or hepatitis C virus infection with a detectable viral load.
- --Note: Patients with an undetectable HBV viral load on appropriate suppressive therapy are eligible. Patients with an undetectable HCV viral load are eligible.
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
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)
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.
Read the detailed 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 heterogeneity in breast cancer. Blockade of CDK4/6 and of lysine deacetylases (DAC) are both promising treatments for breast cancer. DAC inhibitors have been shown to have single-agent activity against triple-negative breast cancer in vivo, possibly through decreasing EMT, decreasing migration, and decreasing metastasis [6, 7] CDK4/6 inhibitor monotherapy causes cell cycle arrest and tumor regression in triple-negative breast cancer models. [8, 9] However, neither approach has been successfully translated into clinical use as a monotherapy.
There are several lines of evidence demonstrating that inhibiting DAC increases the sensitivity of breast cancer to CDK4/6 inhibition. Recently, we showed that inhibitors of cell cycle progression, including CDKN1A, CDKN1C, CDKN2B, and CDKN2D, are increased by DAC inhibition in breast cancer cell lines, including triple-negative cell lines. [10] Others have shown cell cycle arrest by DAC inhibitors due to increases in p21 or decreases in CDK2 and cyclin A. [11-13] We also see an increase in RB1 expression in breast cancer cell lines. In the TCGA breast cancer analysis, RB1 was frequently down-regulated but not mutated or lost in triple-negative breast cancer. [14] Therefore, we hypothesized that DAC inhibition would increase the sensitivity of breast cancer to CDK4/6 inhibition. We first tested this hypothesis in a small panel of cell lines. We showed and published that all showed synergy between a CDK4/6 inhibitor (PD-0322991) and DAC inhibitors. [10] Since then, we have tested the combination of the DAC inhibitor vorinostat and the CDK4/6 inhibitor PD-322991 in a larger panel of cell lines and have shown at least additivity in most triple-negative cell lines. Indeed, it seems that those cancers least sensitive to CDK4/6 inhibition may benefit the most from co-treatment with a DAC inhibitor.
Recently, we investigated ribociclib and belinostat in six triple-negative breast cancer cell lines. All 6 cell lines showed growth inhibition with belinostat and panobinostat. Synergy was seen in four of the six cell lines at multiple doses.
We have also recently completed an analysis on a window of opportunity trial of the DAC inhibitor high-dose valproic acid, in breast cancer.[15] In that study, women were treated with valproic acid for one week before definitive therapy began. Fifty percent of women with triple-negative breast cancers had a significant decrease in Ki-67 with one week of valproic acid, providing proof of principle biologic activity of DAC inhibition in triple-negative breast cancer. (By contrast, no HER2 positive tumor had a decrease in Ki-67 with valproic acid treatment.) Given the genomic similarities between serous ovarian cancer and triple-negative breast cancer seen in the TCGA and pan-cancer analyses [16], we have chosen to include ovarian cancers in the dose-escalation component to increase accrual rate but not in the dose-expansion.
Neither CDK4/6 inhibition nor DAC inhibition have a well-defined predictive biomarker to determine which cancers will respond and which will not. Because of the complex genomic effects of inhibition of the 11 DACs and the multiple targets of DACs, including histones, p53, etc, it is unlikely that a single gene or protein alteration will predict sensitivity. We have published a method for predicting sensitivity to targeted drugs using genome-wide gene expression analysis. [17] After demonstrating proof of principle by accurately predicting sensitivity to vemurafenib, we developed a genomic biomarker for the DAC inhibitor valproic acid. We then validated that this biomarker predicted sensitivity in vitro and in vivo. In the window of opportunity discussed above, our genomic signature had an AUC of 0.66 for predicting decreased Ki-67 with one week of treatment with valproic acid. We will develop a similar multi-gene gene expression based biomarker for the combination of ribociclib and belinostat.
- Being tested
- Ribociclib, Belinostat
- Medical subject headings
- Breast Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibociclibDrug
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
BelinostatDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Ribociclib; Drug: Belinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 28 days after initiation of study treatment
Secondary outcomes (3)
Frequency of Attributed Adverse Events (AEs) and Serious Adverse Events (SAEs)
To assess the safety of ribociclib and belinostat in combination.
This outcome measure will report the count of participants who experienced an Grade 3 or higher Adverse Event (AE) or Serious Adverse Event (SAE) related to ribociclib and belinostat. Events with a Definite, Probable, or Possible attribution were considered attributed to ribociclib and belinostatin.
Measured: up to 5 months from the start of study treatment
Progression Free Survival (PFS)
To assess the efficacy in the study population. Progression-free survival (PFS) is defined as the time from study drug initiation to the time of documented disease progression (as assessed by RECIST 1.1) or death from any cause.
Measured: up to 4 months
Objective Response Rate (ORR)
To assess the efficacy in the study population. Objective response rate is defined as the proportion of patients achieving CR (Complete Response) or PR (Partial Response), as assessed by RECIST 1.1 while on study treatment. CR was defined as a the disappearance of all target lesions and non-target lesions. PR was defined as a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD, for a minimum of four weeks.
Measured: up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2020
- Study start3 May 2021
- Primary completion14 Mar 2024
- Study completion25 Sep 2025
Why it stopped: No accrual in one year
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Acrotech Biopharma, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Theresa Werner, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04315233
- Sponsor's protocol ID
- 130492
- Other IDs
- U54CA209978
- Acronym
- CHARGE
- Status last verified
- May 2026
- First submitted
- 17 Mar 2020
- Last updated
- 4 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04315233
- Acronym / sponsor ID
- CHARGE / 130492
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No accrual in one year
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Novartis, Acrotech Biopharma, National Cancer Institute (NCI)
- Study start
- 3 May 2021 (actual)
- Primary completion
- 14 Mar 2024 (actual)
- Study completion
- 25 Sep 2025 (actual)
- First posted
- 19 Mar 2020 (actual)
- Results
- Posted 4 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 heterogeneity in breast cancer. Blockade of CDK4/6 and of lysine deacetylases (DAC) are both promising treatments for breast cancer. DAC inhibitors have been shown to have single-agent activity against triple-negative breast cancer in vivo, possibly through decreasing EMT, decreasing migration, and decreasing metastasis [6, 7] CDK4/6 inhibitor monotherapy causes cell cycle arrest and tumor regression in triple-negative breast cancer models. [8, 9] However, neither approach has been successfully translated into clinical use as a monotherapy.
There are several lines of evidence demonstrating that inhibiting DAC increases the sensitivity of breast cancer to CDK4/6 inhibition. Recently, we showed that inhibitors of cell cycle progression, including CDKN1A, CDKN1C, CDKN2B, and CDKN2D, are increased by DAC inhibition in breast cancer cell lines, including triple-negative cell lines. [10] Others have shown cell cycle arrest by DAC inhibitors due to increases in p21 or decreases in CDK2 and cyclin A. [11-13] We also see an increase in RB1 expression in breast cancer cell lines. In the TCGA breast cancer analysis, RB1 was frequently down-regulated but not mutated or lost in triple-negative breast cancer. [14] Therefore, we hypothesized that DAC inhibition would increase the sensitivity of breast cancer to CDK4/6 inhibition. We first tested this hypothesis in a small panel of cell lines. We showed and published that all showed synergy between a CDK4/6 inhibitor (PD-0322991) and DAC inhibitors. [10] Since then, we have tested the combination of the DAC inhibitor vorinostat and the CDK4/6 inhibitor PD-322991 in a larger panel of cell lines and have shown at least additivity in most triple-negative cell lines. Indeed, it seems that those cancers least sensitive to CDK4/6 inhibition may benefit the most from co-treatment with a DAC inhibitor.
Recently, we investigated ribociclib and belinostat in six triple-negative breast cancer cell lines. All 6 cell lines showed growth inhibition with belinostat and panobinostat. Synergy was seen in four of the six cell lines at multiple doses.
We have also recently completed an analysis on a window of opportunity trial of the DAC inhibitor high-dose valproic acid, in breast cancer.[15] In that study, women were treated with valproic acid for one week before definitive therapy began. Fifty percent of women with triple-negative breast cancers had a significant decrease in Ki-67 with one week of valproic acid, providing proof of principle biologic activity of DAC inhibition in triple-negative breast cancer. (By contrast, no HER2 positive tumor had a decrease in Ki-67 with valproic acid treatment.) Given the genomic similarities between serous ovarian cancer and triple-negative breast cancer seen in the TCGA and pan-cancer analyses [16], we have chosen to include ovarian cancers in the dose-escalation component to increase accrual rate but not in the dose-expansion.
Neither CDK4/6 inhibition nor DAC inhibition have a well-defined predictive biomarker to determine which cancers will respond and which will not. Because of the complex genomic effects of inhibition of the 11 DACs and the multiple targets of DACs, including histones, p53, etc, it is unlikely that a single gene or protein alteration will predict sensitivity. We have published a method for predicting sensitivity to targeted drugs using genome-wide gene expression analysis. [17] After demonstrating proof of principle by accurately predicting sensitivity to vemurafenib, we developed a genomic biomarker for the DAC inhibitor valproic acid. We then validated that this biomarker predicted sensitivity in vitro and in vivo. In the window of opportunity discussed above, our genomic signature had an AUC of 0.66 for predicting decreased Ki-67 with one week of treatment with valproic acid. We will develop a similar multi-gene gene expression based biomarker for the combination of ribociclib and belinostat.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Dose Escalation Cohort | Experimental | Drug: Ribociclib, Drug: BelinostatRibociclib 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. |
| Cohort 2: Dose expansion cohort | Experimental | Drug: Ribociclib, Drug: BelinostatParticipant 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- 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.
Key exclusion criteria (33 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RibociclibRibociclib 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 | Drug | Cohort 1: Dose Escalation Cohort, Cohort 2: Dose expansion cohort |
| BelinostatBelinostat 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. | Drug | Cohort 1: Dose Escalation Cohort, Cohort 2: Dose expansion cohort |
Primary outcome
Rate of Dose Limiting Toxicity (DLT)
Time frame: up to 28 days after initiation of study treatment
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
3 secondary outcomes
Frequency of Attributed Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: up to 5 months from the start of study treatment
Progression Free Survival (PFS)
Time frame: up to 4 months
Objective Response Rate (ORR)
Time frame: up to 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theresa Werner, MD principal investigator
Huntsman Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ribociclib and Belinostat in people with Metastatic Breast Cancer and Recurrent Ovarian Carcinoma, run by University of Utah at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Dose Limiting Toxicity (DLT) (time frame: up to 28 days after initiation of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.