Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Neuroendocrine

Carcinoma, Small Cell

Neuroendocrine Tumors

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Small Cell Lung Cancer

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Etoposide

Cisplatin

Belinostat

Etoposide phosphate

Enzyme Inhibitors

Histone Deacetylase Inhibitors

Belinostat at 400 mg/m\^2/day plus Cisplatin plus Etoposide

Belinostat at 600 mg/m\^2/day plus Cisplatin plus Etoposide

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

Kimberley J Cooper

Jaydira Del Rivero, M.D.

Kimberley Cooper

NCI Medical Oncology Referral Office

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.

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.

A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity

.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.

Identified as the PK parameter of interest.

Objective response rate will be assessed by CT/MRI scans, calculated by Kaplan-Meier method, reporting the median values of each.

Progression free survival and overall survival calculated by Kaplan-Meier method, reporting the median values of each.

Duration of response will be calculated by the Kaplan-Meier method, starting at date response was identified until progression or the response is declared to have ended, if the participants have a PR or CR.

Spots Global Cancer Trial Database for large cell nec