RECRUITING

A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity

Talk to us

Conditions

Carcinoma, NeuroendocrineTumor, NeuroendocrineTumors, NeuroendocrineNeuroendocrine; CarcinomaSmall Cell; ReceptorsHigh-grade carcinomasResemble small cell carcinomaLarge cell NECHistone DeacetylaseGenotypesNeuroendocrine malignancies

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity

Quick Facts

Study Start:2024-12-26
Study Completion:2028-07-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06406465

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Participants must have histologically confirmed diagnosis of Extrapulmonary High-Grade Neuroendocrine Carcinomas (HGNECs) for which there is no known standard therapy capable of extending life expectancy.
  2. 2. Age \>= 18 years.
  3. 3. Participants with neuroendocrine prostate cancer may continue ongoing LHRH agonist therapy.
  4. 4. Participants with bone metastases or hypercalcemia who began intravenous bisphosphonate treatment prior to study entry may continue this treatment while on study.
  5. 5. Evaluable (measurable or non-measurable) disease, per RECIST 1.1.
  6. 6. ECOG performance status \<=2 at screening
  7. 7. Participants must have adequate organ and marrow function as defined below:
  8. * Leukocytes \>=3,000/mcL
  9. * Hemoglobin \>= 10 g/dL
  10. * Absolute neutrophil count (ANC) \>=1,500/mcL
  11. * Platelets \>=100,000/mcL
  12. * 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
  13. * Total bilirubin \<= 1.5 x institutional upper limit of normal (ULN).
  14. * Serum Creatinine \<= 1.5 X institutional ULN OR
  15. * An estimated Creatinine clearance (CrCL) \>=60 mL/min/1.73 m\^2 based on the Cockcroft Gault equation
  16. * Prothrombin time (PT) / International normalized ratio (INR) and Partial thromboplastin time (PTT) \<= 1 X institutional ULN
  17. 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
  18. 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.
  19. 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).
  20. 11. Willing to comply with study procedures and follow-up.
  21. 12. Participants must be able to understand and be willing to sign a written informed consent document.
  1. 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. 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. 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. 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. 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. 6. Participants with platinum-refractory disease.
  7. 7. Participants who have had another histone deacetylase inhibitor (e.g., valproic acid, vorinostat) for at least 2 weeks prior to enrollment.
  8. 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. 9. Pregnancy (confirmed with beta-Human chorionic gonadotropin (HCG) serum or urine pregnancy test performed in WOCBP at screening)
  10. 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. 11. Participants who have had more than one prior systemic therapy are not eligible
  12. 12. 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.
  13. 13. Participants with HIV infection if CD4 count \<200 cells per cubic millimeter before treatment initiation
  14. 14. Uncontrolled intercurrent illness that would limit compliance with study requirements.

Contacts and Locations

Study Contact

Kimberley J Cooper
CONTACT
(240) 858-7989
kimberley.cooper@nih.gov
Jaydira Del Rivero, M.D.
CONTACT
(240) 858-3851
delriveroj@mail.nih.gov

Principal Investigator

Jaydira Del Rivero, M.D.
PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Jaydira Del Rivero, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-26
Study Completion Date2028-07-30

Study Record Updates

Study Start Date2024-12-26
Study Completion Date2028-07-30

Terms related to this study

Keywords Provided by Researchers

  • High-grade carcinomas
  • Resemble small cell carcinoma
  • Large cell NEC
  • Histone Deacetylase
  • Genotypes
  • Neuroendocrine malignancies

Additional Relevant MeSH Terms

  • Carcinoma, Neuroendocrine
  • Tumor, Neuroendocrine
  • Tumors, Neuroendocrine
  • Neuroendocrine; Carcinoma
  • Small Cell; Receptors