Study of CEP-9722 in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma
This study has been completed.
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Cephalon )
First received: April 19, 2011
Last updated: January 17, 2013
Last verified: January 2013
The primary objective of the study is to determine the maximum tolerated dose (MTD) of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors or mantle cell lymphoma.
Solid Tumors or Mantle Cell Lymphoma
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose-Escalation Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of CEP-9722 (a PARP 1 and PARP 2 Inhibitor) in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors or Mantle Cell Lymphoma|
Resource links provided by NLM:
U.S. FDA Resources
Further study details as provided by Teva Pharmaceutical Industries:
Primary Outcome Measures:
- Determination of the maximum tolerated dose (MTD) of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors or mantle cell lymphoma. [ Time Frame: Baseline and endpoint (as soon as possible after Day 21 of the last cycle) ] [ Designated as safety issue: Yes ]To determine the maximum tolerated dose of CEP-9722, as defined by dose-limiting toxicities (DLTs) reported during the second 21-day treatment cycle (the first cycle of CEP-9722 administration).
Secondary Outcome Measures:
- Evaluate the safety and tolerability of CEP-9722 in combination with gemcitabine and cisplatin [ Time Frame: During the entire study, a minimum of 6 wks (two 21-day cycles) up to a maximum of 18 wks (six 21-day cycles). ] [ Designated as safety issue: Yes ]Assessed by the occurrence of adverse events, clinical laboratory test results, vital signs measurements, electrocardiogram (ECG) findings, physical examination findings, and concomitant medication usage. Creatinine clearance will be calculated according to the Cockroft-Gault formula. An audiogram will be performed at screening and repeated during the study if clinically relevant according to the investigator. Pts who complete or withdraw from treatment will have final procedures/assessments performed as soon as possible, after day 21 of the last cycle, at the end-of-treatment visit.
- Cmax pharmacokinetics parameter [ Time Frame: Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3 ] [ Designated as safety issue: No ]To characterize the pharmacokinetics profile of CEP-8983 (the active moiety of CEP-9722) following administration of CEP-9722, through measurement of the Maximum observed drug Concentration (Cmax).
- AUC pharmacokinetics parameter [ Time Frame: Days 2 and 7 of Cycle 2 and Day 7 of Cycle 3 ] [ Designated as safety issue: No ]To characterize the pharmacokinetics profile of CEP-8983 (the active moiety of CEP-9722) following administration of CEP-9722, through measurement of the Area Under the plasma concentration-time Curve (AUC).
- Pharmacodynamics assessment [ Time Frame: Screening and Day 2 of Cycle 2 at predose, and at 2 and 6 hours after administration of CEP-9722 ] [ Designated as safety issue: No ]To determine the extent of poly-adenosine diphosphate ribose polymerase (PARP) inhibition in peripheral blood mononuclear cells following administration of CEP-9722
- Efficacy - will be assessed by Tumor response evaluation of each patient [ Time Frame: Screening, cycles 3 and 6, and every 2 cycles after cycle 6 until disease progression ] [ Designated as safety issue: No ]Tumor response will be determined using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines, when possible for patients with solid tumors. For patients with mantle tumors, tumor response may be evaluated by the International Working Group criteria.
|Study Start Date:||May 2011|
|Study Completion Date:||January 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: CEP-9722 in combination with Gemcitabine and Cisplatin
Study drugs will be administered in cycles of 21 days for up to 6 cycles. CEP-9722 treatment will be initiated at cycle 2. After cycle 3, patients may discontinue gemcitabine and/or cisplatin for reasons of tolerability, at the discretion of the investigator.
CEP-9722 will be administered orally from day 2 through day 7 of each cycle beginning with cycle 2. The starting dose will be 150 mg twice daily. Following cycle 2, the dose will either be decreased to 150 mg daily or increased to 200 mg twice daily in a cohort of 3 to 4 new patients. Subsequent cycles will increase the dose by 100 mg twice daily in cohorts of 3 to 4 patients (with criteria to expand to 6 patients) to a maximum of 400 mg twice daily. Patients must receive CEP-9722 to remain in the study. Once treatment with CEP-9722 is discontinued, patients will withdraw from the study.Drug: Gemcitabine
Gemcitabine will be administered at 1250 mg/m^2 intravenously on day 1 and day 8 of each 21-day cycle. Dosage reduction may be applied on day 8 (within a cycle) or on day 1 of the next cycle based upon the grade of toxicity experienced by the patient.Drug: Cisplatin
Cisplatin will be administered at 75 mg/m^2 intravenously on day 1 of each cycle, after the infusion of gemcitabine. Dosage reduction may be applied on day 1 of the next cycle based upon the grade of toxicity experienced by the patient.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01345357
|Teva Investigational Site 3|
|Teva Investigational Site 1|
|Teva Investigational Site 2|
Sponsors and Collaborators
|Study Director:||Sponsor's Medical Expert, MD||Cephalon, France|