Ignite Creation Date:
2024-05-11 @ 8:30 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06406465
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-05-08
Brief Title:
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
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 UGT1A128 and UGT1A160 genotypes of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide in participants with neuroendocrine malignancies based on UGT1A128 and UGT1A160 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 n9 carrying UGT1A111 or UGT1A1128 and n30 carrying any other combination of variant alleles at UGT1A128 or UGT1A160
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 400mgm2day for UGT1A12828 or at least one UGT1A160 allele UGT1A128 and UGT1A160 genotypes or 2 600 mgm2day for wild-type participants and those carrying UGT1A1128 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 mgm2 IV on day 2 and etoposide at 80 mgm2 IV daily x3 on days 2 - 4
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 UGT1A128 and UGT1A160 genotypes of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide in participants with neuroendocrine malignancies based on UGT1A128 and UGT1A160 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 n9 carrying UGT1A111 or UGT1A1128 and n30 carrying any other combination of variant alleles at UGT1A128 or UGT1A160
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 400mgm2day for UGT1A12828 or at least one UGT1A160 allele UGT1A128 and UGT1A160 genotypes or 2 600 mgm2day for wild-type participants and those carrying UGT1A1128 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 mgm2 IV on day 2 and etoposide at 80 mgm2 IV daily x3 on days 2 - 4
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001601-C | None | None | None |