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

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