Trials / Recruiting

RecruitingNCT06406465

A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 60 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years – 120 Years
Healthy volunteers: Not accepted

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.

Detailed description

Background: * Extrapulmonary High-Grade Neuroendocrine Neoplasms (HGNENs) are all high-grade neoplasms that may resemble small cell carcinoma or large cell Neuroendocrine Carcinomas (NEC) of the lung. Poorly differentiated NECs are often associated with a rapidly progressive disease and a proliferative rate (Ki67%) \>20%. * As a general rule, poorly differentiated NECs are treated with platinum-based regimens according to small cell carcinoma guidelines. * This protocol will study a continuous infusion of the histone deacetylase (HDAC) inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced neuroendocrine neoplasms. Objective: -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 in participants with neuroendocrine malignancies based on UGT1A1\*28 and UGT1A1\*60 genotypes. Eligibility: * The protocol will be open to participants with Extrapulmonary High-Grade Neuroendocrine Neoplasms (HGNENs) * Participants will be recruited based on genotype, with n=9 carrying UGT1A1\*1/\*1 or UGT1A1\*1/\*28 and n=30 carrying any other combination of variant alleles at UGT1A1\*28 or UGT1A1\*60. * Age \>=18 years * ECOG Performance Status 0-2 Design: * Parallel design in which the starting dose of belinostat is administered as a 48-hour continuous infusion at two possible doses based on genotype: 1) 400mg/m\^2/day for UGT1A1\*28/\*28 or at least one UGT1A1\*60 allele UGT1A1\*28 and UGT1A1\*60 genotypes or 2) 600 mg/m\^2/day for wild-type participants and those carrying UGT1A1\*1/\*28 in the absence of other variant alleles. * To define pharmacokinetics, toxicities of belinostat provided to participants who carry the above genotype groups. * All participants will also receive cisplatin at 60 mg/m\^2 IV on day 2, and etoposide at 80 mg/m\^2 IV daily x3 on days 2 - 4.

Conditions

Interventions

Type	Name	Description
DRUG	Belinostat	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
DRUG	Cisplatin	60 mg/m\^2 IV over 60 minutes on day 2
DRUG	Etoposide	80 mg/m\^2 IV over 60 minutes on day 2 after infusion of cisplatin and again on days 3 and 4

Timeline

Start date: 2026-04-22
Primary completion: 2027-07-30
Completion: 2028-07-30
First posted: 2024-05-09
Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06406465. Inclusion in this directory is not an endorsement.