A Phase I Study of Belinostat in Combination With Cisplatin and Etoposide in Adults With Small Cell Lung Carcinoma and Other Advanced Cancers
- Conditions
- Carcinoma NeuroendocrineSmall Cell Lung CarcinomaMalignant Epithelial Neoplasms
- Interventions
- Registration Number
- NCT00926640
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
BACKGROUND:
* The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. It is thought that the cell death observed with this class of agents may be mediated, in part, through the selective acetylation of histone proteins resulting in increased expression of specific genes.
* For solid tumors in general, cell death in preclinical models has not translated to activity in patients. For this reason, studies increasingly have combined chemotherapy with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer cells.
* This protocol will study a continuous infusion of the HDAC inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced cancer.
OBJECTIVES:
* To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
* Evaluate molecular markers of HDAC inhibition.
ELIGIBILITY:
* The protocol will be open to all patients with recurrent or advanced cancer (small-cell lung cancer and other advanced cancers) for whom standard therapy offers no curative potential.
* Age greater than or equal to 18 years
* ECOG Performance Status 0-2
DESIGN:
* The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV infusion on days 1 and 2, cisplatin at 80 mg/m (2) IV on day 2, and etoposide at 100 mg/m (2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to traditional 3 patient cohorts.
* Treatment schedule and dose escalation schemata.
- Detailed Description
BACKGROUND:
* The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These agents lead to the increased acetylation of both histone and non-histone proteins, which leads to rapid cell death in many tumor models. It is thought that the cell death observed with this class of agents may be mediated, in part, through the selective acetylation of histone proteins resulting in increased expression of specific genes.
* For solid tumors in general, cell death in preclinical models has not translated to activity in patients. For this reason, studies increasingly have combined chemotherapy with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer cells.
* This protocol will study a continuous infusion of the HDAC inhibitor belinostat in combination with cisplatin and etoposide for patients with advanced cancer.
OBJECTIVES:
* To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
* Evaluate molecular markers of HDAC inhibition.
* To explore the results of administering the dose of belinostat based on the patients' UGT1A1 \*28 or \*60 genotype, which is a characteristic that may be associated with toxicity.
ELIGIBILITY:
* The protocol will be open to all patients with recurrent or advanced cancer (small-cell lung cancer and other advanced cancers) for whom standard therapy offers no curative potential.
* Age greater than or equal to 18 years
* ECOG Performance Status 0-2
DESIGN:
* The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV infusion on days 1 and 2, cisplatin at 60 mg/m(2) IV on day 2, and etoposide at 80 mg/ (2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to traditional 3 patient cohorts.
* With Amendment M, dosing will be based on UGT1A1 status, at either 400 mg/m(2) or
600 mg/m(2)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Etoposide Belinostat dose escalation 2 Belinostat Belinostat UGT1A1 wild type/\*28 variant 2 Cisplatin Belinostat UGT1A1 wild type/\*28 variant 2 Etoposide Belinostat UGT1A1 wild type/\*28 variant 3 Belinostat Belinostat UGT1A1\*60 or 2/3/4 variant 3 Cisplatin Belinostat UGT1A1\*60 or 2/3/4 variant 1 Belinostat Belinostat dose escalation 3 Etoposide Belinostat UGT1A1\*60 or 2/3/4 variant 1 Cisplatin Belinostat dose escalation
- Primary Outcome Measures
Name Time Method Safety and tolerability Dose Limiiting Toxicity
- Secondary Outcome Measures
Name Time Method Increased acetylation in PBMCs End of treatment Markers of HDAC End of treatment Tumor response Disease Progression miRNA and CGH End of treatment
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States