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

NCT ID: NCT00700336

Last Updated: 2021-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2012-11-30

Brief Summary

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.

Detailed Description

This is an open-label, multicenter, international, phase I-II study. The phase I part, a dose-finding study of escalating doses of CBP501 combined with fixed full-dose cisplatin and pemetrexed, has been completed and results are presented in this report. MTD was determined on DLT occurring during the first cycle. This phase I part was evaluated in a patient population with advanced solid tumors The phase II part will evaluate full-dose cisplatin and pemetrexed combined with CBP501 at the MTD determined in the phase I part. Patients will be randomized in a 2:1 ratio to pemetrexed, cisplatin and CBP501 (Arm A) or pemetrexed and cisplatin (Arm B). This phase II part will be evaluated in chemotherapy-naïve patients with malignant pleural mesothelioma

Randomization will be stratified by:

• Histology: epithelial vs other (sarcomatoid or biphasic)
• Performance status: 0-1 vs 2

Conditions

Malignant Pleural Mesothelioma; Solid Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pemetrexed, Cisplatin, and CBP501: Phase 2

pemetrexed, cisplatin and CBP501

Group Type: EXPERIMENTAL

pemetrexed, cisplatin and CBP501

Intervention Type: DRUG

CBP501 25 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 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.

Pemetrexed and Cisplatin: Phase 2

pemetrexed and cisplatin

Group Type: ACTIVE_COMPARATOR

pemetrexed and cisplatin

Intervention Type: DRUG

Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 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.

Pemetrexed, Cisplatin, and CBP501:Phase 1

MTD, which was equal to recommended dose for the Phase II part, was determined by 6 patients (3+3)

Group Type: EXPERIMENTAL

pemetrexed, cisplatin and CBP501, dose finding

Intervention Type: DRUG

Dose level 1: CBP501 16 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 Dose level 2: CBP501 25 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 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.

Interventions

pemetrexed, cisplatin and CBP501

CBP501 25 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 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.

Intervention Type: DRUG

pemetrexed and cisplatin

Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 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.

Intervention Type: DRUG

pemetrexed, cisplatin and CBP501, dose finding

Dose level 1: CBP501 16 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 Dose level 2: CBP501 25 mg/m2, Pemetrexed 500 mg/m2, cisplatin 75 mg/m2 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.

Intervention Type: DRUG

Other Intervention Names

Arm A; Arm B; Phase I part; Dose finding

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CanBas Co. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lee Krug

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Mayo Clinic

Scottsdale, Arizona, United States

Arizona Cancer Center

Tucson, Arizona, United States

City of Hope

Duarte, California, United States

University of Chicago

Chicago, Illinois, United States

Karmanos Cancer Institute/Wayne State University

Detroit, Michigan, United States

Nevada Cancer Institute

Las Vegas, Nevada, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Memorial-Sloan Kettering Cancer Center

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Penn State Milton S. Hershey Medical Ctr.

Hershey, Pennsylvania, United States

Cancer Therapy & Research Center

San Antonio, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Sha SK, Sato T, Kobayashi H, Ishigaki M, Yamamoto S, Sato H, Takada A, Nakajyo S, Mochizuki Y, Friedman JM, Cheng FC, Okura T, Kimura R, Kufe DW, Vonhoff DD, Kawabe T. Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint. Mol Cancer Ther. 2007 Jan;6(1):147-53. doi: 10.1158/1535-7163.MCT-06-0371.

Reference Type: BACKGROUND

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Matsumoto Y, Shindo Y, Takakusagi Y, Takakusagi K, Tsukuda S, Kusayanagi T, Sato H, Kawabe T, Sugawara F, Sakaguchi K. Screening of a library of T7 phage-displayed peptides identifies alphaC helix in 14-3-3 protein as a CBP501-binding site. Bioorg Med Chem. 2011 Dec 1;19(23):7049-56. doi: 10.1016/j.bmc.2011.10.004. Epub 2011 Oct 7.

Reference Type: BACKGROUND

PMID: 22032894 (View on PubMed)

Other Identifiers

CBP08-01

Identifier Type: -

Identifier Source: org_study_id