NCT00899054

Safety and Efficacy Study of P276-00 in Combination With Radiation in Subjects With Advanced Head and Neck Cancer

An Open Label, Multicenter Phase I/II Study Of Selective Cyclin Dependent Kinase Inhibitor P276-00 In Combination With Radiation In Subjects With Recurrent And/Or Locally Advanced Squamous Cell Carcinoma Of Head And Neck

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Piramal Enterprises Limited · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to identify a dose of P276-00 that can be safely administered along with Radiation and to examine safety and efficacy of the combination in treatment of advanced head and neck cancer.

Detailed description

This is an open label single arm multicenter trial to evaluate safety and efficacy of P276-00 in combination with radiation in patients with recurrent and/or locally advanced squamous cell carcinoma of head and neck. The Primary objective of this study is to determine maximum tolerated dose (MTD) and dose limiting toxicity (ies) (DLT/s) of P276-00 in combination with radiation in subjects with recurrent and/or locally advanced squamous cell carcinoma of head and neck (SCCHN). The Secondary objectives are 1. To evaluate safety and tolerability of the combination regimen of P276-00 and radiation in the study population 2. To analyze pharmacokinetics (PK) of P276-00 in the study population 3. To evaluate efficacy of the combination regimen of P276-00 and radiation in the study population 4. To perform exploratory analysis of biomarkers associated with use of P276-00 and radiation in the study population. In phase 1 component,a cohort of 3 subjects will be enrolled at starting dose level of P276-00 which is 100 mg/m2/day to be given intravenously from day 1 to day 5 in 21 day cycle for 2 cycles in combination with radiation. If this dose is well tolerated then next cohort will be enrolled at higher dose level of P276-00. P276-00 dose escalation will continue until MTD of P276-00 in combination with Radiation is determined. The subsequent dose levels of P276-00 will be 140 mg/m2/day and 185 mg/m2/day. In phase 2 component 10 subjects will be enrolled at this MTD of P276-00 in combination with radiation to evaluate efficacy. Dose of radiation for both phases is 60 Gy over 6 weeks. Safety evaluations will be conducted at regular intervals during the study. Tumor measurements will be undertaken at baseline, at the end of cycle 2 and 5 to 6 weeks after end of cycle 2. Response evaluation will be performed by Response Evaluation Criteria in Solid Tumors (RECIST). Subjects showing stable disease or better response at the last assessment will be followed up for tumor measurements until progression or recurrence of disease.

Conditions

• Squamous Cell Carcinoma of Head and Neck

Interventions

Type	Name	Description
DRUG	P276-00	P276-00 will be administered at different dose levels: level 1: 100 mg/m2/day dose level 2: 140 mg/m2/day dose level 3: 185 mg/m2/day to be given from day 1 to day 5 every 21 days for 2 cycle. P276-00 will be administered as intravenous infusion in 200 ml 5% Dextrose over 30 min from days 1 to 5 per 21 day cycle for two cycles.
RADIATION	External beam radiotherapy (EBRT)	All subjects will receive external beam radiotherapy (EBRT)by using standard conventional fractionation i.e. 2 Gy per day for 5 days a week for a total radiation dose of 60 Gy over 6 weeks followed by upto 10 additional Gy if required.

Timeline

• Start date: 2009-08-01
• Primary completion: 2011-01-01
• Completion: 2012-11-01
• First posted: 2009-05-12
• Last updated: 2012-11-22

Locations

6 sites across 1 country: India