A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
2 other identifiers
interventional
60
1 country
1
Brief Summary
Background: High-grade neuroendocrine carcinomas (HGNEC) are cancers that develop in different parts of the body, including the digestive tract, genitals, neck, and head. One drug (belinostat), combined with 2 other drugs (etoposide and cisplatin), is approved to treat HGNEC. But some people may have a gene variant that affects how quickly their body gets rid of the drug; these people may do better with different dosages of belinostat. Objective: To test higher or lower doses of belinostat based on gene variants in people with HGNEC. Eligibility: People aged 18 years and older with HGNEC. Design: Participants will be screened. They will have a physical exam with blood tests. Some blood will be used for genetic testing. They will have imaging scans and a test of their heart function. Samples of tumor tissue may be collected. All 3 study drugs (belinostat, etoposide, cisplatin) are given through a tube attached to a needle inserted into a vein. Treatment will be given in 21-day cycles. For cycles 1 through 6: Participants will come to the clinic for the first 4 days. They will be given all 3 drugs. Imaging scans and other tests will be repeated. Each visit will last 4 to 8 hours. After cycle 6: Participants may continue treatment with belinostat alone. They will come to the clinic for the first 3 days of each cycle. They may continue treatment for up to 5 years if the drug is helping them. Participants will have a follow-up visit 30 days after their last dose of belinostat. Then they will receive follow-up visits by phone or email every 3 to 6 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 8, 2024
CompletedFirst Posted
Study publicly available on registry
May 9, 2024
CompletedStudy Start
First participant enrolled
April 21, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 30, 2027
Study Completion
Last participant's last visit for all outcomes
July 30, 2028
April 16, 2026
January 15, 2026
1.3 years
May 8, 2024
April 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To determine if pharmacogenomic intervention can normalize the area under the curve (AUC) at cycle 6 between UGT1A1*28 and UGT1A1*60 genotypes) of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide
Identified as the PK parameter of interest.
Cycles 1-6 pre- and post- treatment with belinostat with all doses
Secondary Outcomes (4)
To determine efficacy with respect to objective response rate of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide
Every 9 weeks while on study therapy
To determine the progression-free survival (PFS) and overall survival (OS) of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide
PFS will be assessed from on-study date until date of progression or death without progression. Overall survival (OS) will be calculated from the on-study date until date of death. Until 3 years after last participant enrolled.
To assess duration of response of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide in platinum sensitive
Until progression or the response is declared to have ended , if the participants have a PR or CR. Until 3 years after last participant enrolled.
To assess duration of response of belinostat maintenance
Every 9 weeks while on monotherapy. Total study therapy will not exceed 5 years.
Study Arms (2)
Arm 1
EXPERIMENTALBelinostat at 400 mg/m\^2/day plus Cisplatin plus Etoposide
Arm 2
EXPERIMENTALBelinostat at 600 mg/m\^2/day plus Cisplatin plus Etoposide
Interventions
400mg/m\^2/24h or 600 mg/m\^2/24h IV over (48h continuous infusion) on days 1, 2 and 3 based on UGT1A1 status
80 mg/m\^2 IV over 60 minutes on day 2 after infusion of cisplatin and again on days 3 and 4
Eligibility Criteria
You may qualify if:
- Participants must have histologically confirmed diagnosis of Extrapulmonary High-Grade Neuroendocrine Neoplasms (HGNENs) for which there is no known standard therapy capable of extending life expectancy.
- Age \>= 18 years.
- Participants with neuroendocrine prostate cancer may continue ongoing LHRH agonist therapy.
- Participants with bone metastases or hypercalcemia who began intravenous bisphosphonate treatment prior to study entry may continue this treatment while on study.
- Evaluable (measurable or non-measurable) disease, per RECIST 1.1.
- ECOG performance status \<=2 at screening
- Participants must have adequate organ and marrow function as defined below:
- Leukocytes \>=3,000/mcL
- Hemoglobin \>= 10 g/dL
- Absolute neutrophil count (ANC) \>=1,500/mcL
- Platelets \>=100,000/mcL
- Aspartate aminotransferase (AST) or serum glutamic-oxaloacetic transaminase (SGOT) / Alanine aminotransferase (ALT) or serum glutamic-pyruvic transaminase (SGPT): \<=3 X institutional upper limit of normal
- Total bilirubin \<= 1.5 x institutional upper limit of normal (ULN).
- NOTE: In participants with Gilbert s syndrome, a total bilirubin \<= 3.0 X ULN is allowed
- Serum Creatinine \<= 1.5 X institutional ULN OR
- +7 more criteria
You may not qualify if:
- Participants with prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 14 days prior to the first drug administration. Additionally, FDA-approved hormonal therapy for the treatment or prevention of other malignancies (e.g., breast cancer, prostate cancer) may be continued where in the opinion of the investigator stopping such therapies may increase the risk of disease progression. Potential drug-drug interactions with the hormonal agent will be assessed by the investigator prior to enrollment.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to belinostat, cisplatin, etoposide or other agents used in study. Participants with a history of allergic reactions to medications containing polysorbate 80 will be evaluated on a case-by-case basis.
- Participants with treated brain metastases are not eligible except if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
- Participants who have not recovered (CTCAE \<= grade 1) from non heme adverse events due to prior treatments, except for alopecia, or stable grade 2 tinnitus (not interfering with ADL's) or baseline hearing loss by audiometry or stable grade 2 sensory neuropathy (moderate symptoms; limiting instrumental ADL) without pain or motor component, and not interfering with ADL's.
- Participants taking strong UGT1A1 inhibitors or CYP3A4 inhibitors or inducers must discontinue their use a minimum of 5 half-lives prior to starting treatment on this trial
- Participants with platinum-refractory disease.
- Participants who have had another histone deacetylase inhibitor (e.g., valproic acid, vorinostat) for at least 2 weeks prior to enrollment.
- Participants who have had radiation to the pelvis or other bone marrow-bearing sites will be considered on a case-by-case basis and may be excluded if the bone marrow reserve is not considered adequate (\>25% of bone marrow).
- Pregnancy (confirmed with beta-Human chorionic gonadotropin (HCG) serum or urine pregnancy test performed in WOCBP at screening)
- Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia, or a need for anti-arrhythmic therapy (use of medication to control heart rate in participants with atrial fibrillation is allowed, if stable medication for at least last month prior to enrollment and medication not listed as causing Torsade de Points), or evidence of acute ischemia on ECG.
- Baseline prolongation of QT/QTc interval, i.e., defined as an average QTc interval \> 450 msec calculated using the Fridericia formula for QT correction; Long QT Syndrome; or the required use of concomitant medication that may cause Torsade de Pointes.
- Participants with HIV infection if CD4 count \<200 cells per cubic millimeter before treatment initiation
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jaydira Del Rivero, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 8, 2024
First Posted
May 9, 2024
Study Start (Estimated)
April 21, 2026
Primary Completion (Estimated)
July 30, 2027
Study Completion (Estimated)
July 30, 2028
Last Updated
April 16, 2026
Record last verified: 2026-01-15
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data will be available during the study and indefinitely.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing. @@@@@@@@@@@@This study will comply with the NIH Genomic Data Sharing (GDS) Policy, which applies to all new and ongoing NIH IRP-funded research, as of January 25, 2015, that generates large-scale human or non-human genomic data, as well as the use of these data for subsequent research. Large-scale data include genome-wide association studies (GWAS), single nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data.