A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type

Interventional

Phase

Phase 2

Age range

18 years - 120 years

Sex eligible

All sexes

Healthy volunteers

Not accepted

Participants

60 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

-INCLUSION CRITERIA:

1. 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.
2. Age \>= 18 years.
3. Participants with neuroendocrine prostate cancer may continue ongoing LHRH agonist therapy.
4. Participants with bone metastases or hypercalcemia who began intravenous bisphosphonate treatment prior to study entry may continue this treatment while on study.
5. Evaluable (measurable or non-measurable) disease, per RECIST 1.1.
6. ECOG performance status \<=2 at screening
7. 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
* An estimated Creatinine clearance (CrCL) \>=60 mL/min/1.73 m\^2 based on the Cockcroft Gault equation
* Prothrombin time (PT) / International normalized ratio (INR) and Partial thromboplastin time (PTT) \<= 1 X institutional ULN
8. Hepatitis B virus (HBV)-infected participants can be enrolled if HBV DNA is undetectable. Hepatitis C virus (HCV)-infected participants can be enrolled if HCV RNA level is undetectable
9. Women of child-bearing potential (WOCBP) must agree to use effective contraception (hormonal, intrauterine device (IUD), tube ligation, a partner has had a previous vasectomy, abstinence) prior to study entry, during the study, and for 14 months for women after the last dose of the study drug(s). Men with partners of childbearing potential must agree to use effective contraception (abstinence, condoms, previous vasectomy) or request partners to use effective contraception (per above) during the study and for 11 months after the last dose of study therapy.
10. Breastfeeding participants must be willing to discontinue breastfeeding starting with prior to study entry, during the study, and for 3 months after the last dose of the study drug(s).
11. Willing to comply with study procedures and follow-up.
12. Participants must be able to understand and be willing to sign a written informed consent document.

EXCLUSION CRITERIA:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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
6. Participants with platinum-refractory disease.
7. Participants who have had another histone deacetylase inhibitor (e.g., valproic acid, vorinostat) for at least 2 weeks prior to enrollment.
8. 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).
9. Pregnancy (confirmed with beta-Human chorionic gonadotropin (HCG) serum or urine pregnancy test performed in WOCBP at screening)
10. 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.
11. 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.
12. Participants with HIV infection if CD4 count \<200 cells per cubic millimeter before treatment initiation
13. Uncontrolled intercurrent illness that would limit compliance with study requirements.

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment

Not randomized

Masking

No masking

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Secondary measures

Research locations (1)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

1 locations

Study team and timeline

Lead sponsor

National Cancer Institute (NCI)

Study start

Nov 15, 2026 Estimated

Primary completion

Jul 30, 2027 Estimated

Study completion

Jul 30, 2028 Estimated

First posted

May 9, 2024 Actual

Last updated

Nov 10, 2026 Actual

Official study contacts