A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity

Carcinoma, Neuroendocrine Clinical Trial

Official title: A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity

Status Not yet recruiting

Clinical Trial 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.

Clinical Trial Description

Background:

• Poorly differentiated neuroendocrine carcinomas (NECs) are all high-grade carcinomas that resemble small cell carcinoma or large cell 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 carcinomas.

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 Carcinomas (HGNECs)

• Participants must not have received more than one prior systemic therapy

• 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/m2 IV on day 2, and etoposide at 80 mg/m^2 IV daily x3 on days 2 - 4. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Neuroendocrine
• Neuroendocrine Tumors

• NCT number: NCT06406465
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Kimberley J Cooper
• Phone: (240) 858-7989
• Email: kimberley.cooper@nih.gov
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 26, 2024
• Completion date: July 30, 2028