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Study of CBP501 + Pemetrexed + Cisplatin in Patients With Solid Tumors (Phase I) and Patients With Malignant Pleural Mesothelioma (Phase II)
This study is currently recruiting participants.
Verified by CanBas Co. Ltd., January 2009
Sponsored by: CanBas Co. Ltd.
Information provided by: CanBas Co. Ltd.
ClinicalTrials.gov Identifier: NCT00700336
  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.


Condition Intervention Phase
Malignant Pleural Mesothelioma
MPM
Solid Tumors
Drug: pemetrexed, cisplatin and CBP501
Drug: pemetrexed and cisplatin
Phase I
Phase II

MedlinePlus related topics: Cancer Mesothelioma
Drug Information available for: Cisplatin Pemetrexed disodium Pemetrexed Dextrose Sodium chloride Chlorides
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment
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

Further study details as provided by CanBas Co. Ltd.:

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 ]

Estimated Enrollment: 72
Study Start Date: May 2008
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A: Experimental
pemetrexed, cisplatin and CBP501
Drug: pemetrexed, cisplatin and CBP501

CBP501 for injection is provided in single dose vials (20 mg) containing a sterile lyophilized powder comprising CBP501 peptide acetate salt (peptide base units). For administration, vial contents are reconstituted in 5% Dextrose Injection, USP, and added to a 100 mL IV bag of 5% Dextrose Injection, USP.

Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL.

Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.

Arm B: Active Comparator
pemetrexed and cisplatin
Drug: pemetrexed and cisplatin

Pemetrexed: A commercial formulation of pemetrexed will be used, with reconstitution in 20mL 0.9% sodium chloride solution for injection, then dilution to 100mL.

Cisplatin: A commercial formulation will be used and will be diluted in 250 mL of normal saline for administration.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent obtained prior to initiation of any study-specific procedures
  2. Phase I: 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

    Phase II: Histologically or cytologically confirmed diagnosis of malignant pleural mesothelioma (MPM), not amenable for radical resection, who has not received previous chemotherapy or other systemic treatment

  3. Measurable disease according to the modified Response Evaluation Criteria in Solid Tumors (RECIST, see below)
  4. Male or female patients aged at least 18 years
  5. ECOG Performance Status (PS): 0-2
  6. Previous anticancer treatment must be discontinued at least 3 weeks prior to first dose of study treatment (6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, with the exception of 8 weeks for bicalutamide)
  7. Life expectancy greater than 3 months
  8. Adequate organ function
  9. Female patients of child-bearing potential must have a negative pregnancy test and be using at least one form of contraception as approved by the Investigator for 4 weeks prior to the study and 4 months after the last dose of study drug. For the purposes of this study, child-bearing potential is defined as: "All female patients unless they are post-menopausal for at least one year or are surgically sterile"
  10. Male patients must use a form of barrier contraception approved by the investigator during the study and for 4 months after the last dose of study drug
  11. Ability to cooperate with the treatment and follow-up

Exclusion Criteria:

  1. Radiation therapy to more than 30% of the bone marrow prior to entry into the study
  2. Phase II only: Mesothelioma originating outside the pleura (e.g.: peritoneum)
  3. Absence of measurable lesions
  4. The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator.
  5. Any previous history of another malignancy within 5 years of study entry (other than cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix)
  6. Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance
  7. Evidence of peripheral neuropathy > grade 1 according to NCI-CTCAE Version 3
  8. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to study entry
  9. Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception
  10. Known HIV, HBV, HCV infection
  11. Presence of CNS metastases
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00700336

Locations
United States, Nevada
Nevada Cancer Institute Recruiting
Las Vegas, Nevada, United States, 89135
Contact: Sunil Sharma, MD     702-822-5433        
Principal Investigator: Sunil Sharma, MD            
United States, New Mexico
University of New Mexico Cancer Center Recruiting
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 Recruiting
New York, New York, United States, 10022
Contact: Lee M Krug, MD     212-639-8420        
Principal Investigator: Lee M Krug, MD            
United States, Pennsylvania
Penn State Milton S. Hershey Medical Ctr. Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Chandra Belani     717-531-5471        
Principal Investigator: Chandra Belani, MD            
United States, Texas
Cancer Therapy & Research Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Mita C Alain, MD     210-450-5094        
Contact: Tony Carmona     210-450-5979     Carmona@uthscsa.edu    
Principal Investigator: Alain C Mita, MD, MSc            
Sponsors and Collaborators
CanBas Co. Ltd.
  More Information

Responsible Party: CanBas Co. Ltd ( Takumi Kawabe, MD/CEO )
Study ID Numbers: CBP08-01
Study First Received: June 16, 2008
Last Updated: January 9, 2009
ClinicalTrials.gov Identifier: NCT00700336  
Health Authority: United States: Food and Drug Administration

Keywords provided by CanBas Co. Ltd.:
malignant pleural mesothelioma
MPM
solid tumors

Study placed in the following topic categories:
Folic Acid
Pemetrexed
Cisplatin
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Neoplasms, Mesothelial
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Folic Acid Antagonists
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009