Triplet Combination Study

Trial NCT00700336

Official Title: Phase I/II Study of a Triplet Combination of CBP501, Pemetrexed and Cisplatin in Patients With Advanced Solid Tumors and in Chemotherapy-naïve Patients With Malignant Pleural Mesothelioma Purpose: The phase I part of the study is a dose-finding study of escalating doses of CBP501 combined with full-dose cisplatin and pemetrexed in patients with histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or would otherwise be eligible for cisplatin and pemetrexed as first-line therapy. The maximum tolerated dose (MTD) will be determined based on DLTs occurring during the first treatment cycle. Pharmacokinetics of the triplet combination will be assessed during the phase I part of the trial. The phase II part will evaluate full-dose cisplatin and pemetrexed combined with CBP501 (at the MTD determined in the phase I part) in previously untreated, unresectable malignant pleural mesothelioma patients. Patients will be randomized in a 2 : 1 ratio to pemetrexed, cisplatin and CBP501 (Arm A) or to pemetrexed and cisplatin (Arm B); randomization will be stratified according to histology and performance status. Eligibility: Male and female mesothelioma patients 18 years of age or older. Study Design:
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Open Label
  • Primary Purpose: Treatment
Primary Outcome Measures:
  • Ph I: To determine the MTD of CBP501 + pemetrexed + cisplatin in patients with advanced solid tumors. Ph II: To evaluate the efficacy and safety profile of CBP501 + pemetrexed + cisplatin in patients with malignant pleural mesothelioma [ Time Frame: End of study ] [ Designated as safety issue: Yes]
Secondary Outcome Measures:
  • Ph I: To determine the recommended CBP501 dose for exploration in the phase II part [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
  • Ph I: To undertake a preliminary characterization of the safety profile of the triplet combination [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
  • Ph I: Determine the pharmacokinetics of CBP501 when co-administered with cisplatin and pemetrexed and investigate any potential interactions [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Ph I: To evaluate the pharmacodynamics of the triplet combination [ Time Frame: End of study ] [ Designated as safety issue: No]
  • Ph II: To characterize the efficacy according to Modified RECIST criteria, of cisplatin combined with pemetrexed in this patient population and to aid in formulation of the hypothesis for an eventual phase III trial [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Ph II: To evaluate clinical benefit of patients [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
  • Ph II: To evaluate the pharmacodynamics of the combination [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Ph II: Determine the pharmacokinetics of CBP501 when co-administered with cisplatin and pemetrexed and investigate any potential interactions (only in cycle 1 of the first 6 patients in each arm in the US only) [ Time Frame: End of study ] [ Designated as safety issue: No ]
Dates and Locations:
  • Study Start Date: May 2008
  • Estimated Primary Completion Date: April 2012
United States, Arizona Mayo Clinic Scottsdale, Arizona, United States Contact: Helen Ross, MD     480-301-4976 Contact: Heidi Kogut     480-301-4976 Principal Investigator: Helen Ross, MD Arizona Cancer Center Tucson, Arizona, United States Contact: Lorraine Rudzitis     520-626-9001 Principal Investigator: Linda Garland, MD United States, California City of Hope Duarte, California, United States Contact: Marianna Koczywas, MD     626-301-8393 Contact: Emilia Reorizo     626-301-8393 Principal Investigator: Marianna Koczywas, MD United States, Illinois University of Chicago Chicago, Illinois, United States Contact: Hedy Kindler, MD     773-702-1668 Contact: Victoria Blake     (773) 702-1668 Principal Investigator: Hedy Kindler, MD United States, Michigan Karmanos Cancer Institute/Wayne State University Detroit, Michigan, United States Contact: Maureen Kelly     313-578-4405 Principal Investigator: Antoinette Wozniak, MD United States, Nevada Nevada Cancer Institute Las Vegas, Nevada, United States, 89135 Contact: John Ruckdeschel, MD     702-822-5433 Principal Investigator: John Ruckdeschel, MD United States, New Mexico University of New Mexico Cancer Center Albuquerque, New Mexico, United States, 87131 Contact: Claire Verschraegen     505-272-6760 Principal Investigator: Claire Verschraegen, MD United States, New York Memorial-Sloan Kettering Cancer Center New York, New York, United States, 10022 Contact: Lee M Krug, MD     212-639-8420 Principal Investigator: Lee M Krug, MD United States, Ohio Cleveland Clinic Cleveland, Ohio, United States Contact: Cristina Rodriguez, MD     216-444-9452 Principal Investigator: Cristina Rodriguez, MD United States, Pennsylvania Penn State Milton S. Hershey Medical Ctr. Hershey, Pennsylvania, United States, 17033 Contact: Chandra Belani     717-531-5471 Principal Investigator: Chandra Belani, MD United States, Texas Cancer Therapy & Research Center San Antonio, Texas, United States, 78229 United States, Utah Huntsman Cancer Institute Salt Lake City, Utah, United States Contact: Sunil Sharma, MD     801-587-4779 Principal Investigator: Sunil Sharma, MD Reference: