Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
CanBas Co. Ltd.
ClinicalTrials.gov Identifier:
NCT00700336
First received: June 16, 2008
Last updated: December 19, 2012
Last verified: October 2011
  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
Solid Tumors
Drug: pemetrexed, cisplatin and CBP501
Drug: pemetrexed and cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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 ]

Enrollment: 71
Study Start Date: May 2008
Study Completion Date: November 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
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.

Other Name: (ALIMTA)
Active Comparator: Arm B
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.

Other Name: (ALIMTA)

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00700336

Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States
Arizona Cancer Center
Tucson, Arizona, United States
United States, California
City of Hope
Duarte, California, United States
United States, Illinois
University of Chicago
Chicago, Illinois, United States
United States, Michigan
Karmanos Cancer Institute/Wayne State University
Detroit, Michigan, United States
United States, Nevada
Nevada Cancer Institute
Las Vegas, Nevada, United States, 89135
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87131
United States, New York
Memorial-Sloan Kettering Cancer Center
New York, New York, United States, 10022
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States
United States, Pennsylvania
Penn State Milton S. Hershey Medical Ctr.
Hershey, Pennsylvania, United States, 17033
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
Sponsors and Collaborators
CanBas Co. Ltd.
  More Information

Publications:

Responsible Party: CanBas Co. Ltd.
ClinicalTrials.gov Identifier: NCT00700336     History of Changes
Other Study ID Numbers: CBP08-01
Study First Received: June 16, 2008
Last Updated: December 19, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 18, 2014