Carcinoma, NeuroendocrinePhase 2NCT06406465
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
A Phase 2 study testing Belinostat, Cisplatin and Etoposide in people with Carcinoma, Neuroendocrine and Tumor, Neuroendocrine, run by National Cancer Institute (NCI) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Carcinoma, Neuroendocrine, Tumor, Neuroendocrine, Tumors, Neuroendocrine
- What is being tested?
- Belinostat, Cisplatin and Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2026to 30 Jul 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
- 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.
- 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.
- 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.
- 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
- Participants with platinum-refractory disease.
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- Participants who have had another histone deacetylase inhibitor (e.g., valproic acid, vorinostat) for at least 2 weeks prior to enrollment.
- 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).
- Pregnancy (confirmed with beta-Human chorionic gonadotropin (HCG) serum or urine pregnancy test performed in WOCBP at screening)
- 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.
- 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.
- Participants with HIV infection if CD4 count <200 cells per cubic millimeter before treatment initiation
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Anna Rivero, 240-858-7946, anna.rivero@nih.gov
NCI Medical Oncology Referral Office, (240) 760-6050, ncimo_referrals@mail.nih.gov
About this study
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.
Read more
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.
Read the 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
- Carcinoma, Neuroendocrine, Tumor, Neuroendocrine, Tumors, Neuroendocrine, Neuroendocrine; Carcinoma, Small Cell; Receptors
- Keywords
- High-grade carcinomas, Resemble small cell carcinoma, Large cell NEC, Histone Deacetylase, Genotypes, Neuroendocrine malignancies
- Medical subject headings
- Carcinoma, Neuroendocrine, Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelinostatDrug
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
CisplatinDrug
60 mg/m^2 IV over 60 minutes on day 2
EtoposideDrug
80 mg/m^2 IV over 60 minutes on day 2 after infusion of cisplatin and again on days 3 and 4
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Belinostat at 400 mg/m^2/day plus Cisplatin plus Etoposide Receives: Drug: Belinostat; Drug: Cisplatin; Drug: Etoposide |
| Arm 2 | Experimental | Belinostat at 600 mg/m^2/day plus Cisplatin plus Etoposide Receives: Drug: Belinostat; Drug: Cisplatin; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Identified as the PK parameter of interest.
Measured: Cycles 1-6 pre- and post- treatment with belinostat with all doses
Secondary outcomes (4)
To determine efficacy with respect to objective response rate of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide
Objective response rate will be assessed by CT/MRI scans, calculated by Kaplan-Meier method, reporting the median values of each.
Measured: Every 9 weeks while on study therapy
To determine the progression-free survival (PFS) and overall survival (OS) of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide
Progression free survival and overall survival calculated by Kaplan-Meier method, reporting the median values of each.
Measured: PFS will be assessed from on-study date until date of progression or death without progression. Overall survival (OS) will be calculated from the on-study date until date of death. Until 3 years after last participant enrolled.
To assess duration of response of belinostat administered as a continuous 48 h infusion in combination with cisplatin and etoposide in platinum sensitive
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.
Measured: Until progression or the response is declared to have ended , if the participants have a PR or CR. Until 3 years after last participant enrolled.
To assess duration of response of belinostat maintenance
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.
Measured: Every 9 weeks while on monotherapy. Total study therapy will not exceed 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2024
- Study start28 Oct 2026 (estimated)
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, NeuroendocrineStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jaydira Del Rivero, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06406465
- Sponsor's protocol ID
- 10001601
- Other IDs
- 001601-C
- Status last verified
- 15 Jan 2026
- First submitted
- 8 May 2024
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.