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

NCT00700336 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CBP08-01
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 12

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.

Conditions

Malignant Pleural Mesothelioma; Solid Tumors

Keywords

malignant pleural mesothelioma; solid tumors

Outcome Measures

Primary Outcomes (1)

• 4M PFS Rate of Patients With Previously Untreated, Unresectable Malignant Pleural Mesothelioma (MPM) Treated With CBP501, Pemetrexed and Cisplatin

  Planned: Forty-two patients were to be treated in Arm A. If ≥ 23 patients (\>54%) were free of progression and death at 4 months, then the study regimen would be considered for further evaluation in this indication.

  End of study

Study Arms (3)

Pemetrexed, Cisplatin, and CBP501: Phase 2

EXPERIMENTAL

pemetrexed, cisplatin and CBP501

Drug: pemetrexed, cisplatin and CBP501

Pemetrexed and Cisplatin: Phase 2

ACTIVE COMPARATOR

pemetrexed and cisplatin

Drug: pemetrexed and cisplatin

Pemetrexed, Cisplatin, and CBP501:Phase 1

EXPERIMENTAL

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

Drug: pemetrexed, cisplatin and CBP501, dose finding

Interventions

pemetrexed, cisplatin and CBP501 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.

Also known as: Arm A

Pemetrexed, Cisplatin, and CBP501: Phase 2

pemetrexed and cisplatin 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.

Also known as: Arm B

Pemetrexed and Cisplatin: Phase 2

pemetrexed, cisplatin and CBP501, dose finding 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.

Also known as: Phase I part, Dose finding

Pemetrexed, Cisplatin, and CBP501:Phase 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent obtained prior to initiation of any study-specific procedures
• 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
• Measurable disease according to the modified Response Evaluation Criteria in Solid Tumors (RECIST, see below)
• Male or female patients aged at least 18 years
• ECOG Performance Status (PS): 0-2
• 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)
• Life expectancy greater than 3 months
• Adequate organ function
• 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"
• 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
• Ability to cooperate with the treatment and follow-up

You may not qualify if:

• Radiation therapy to more than 30% of the bone marrow prior to entry into the study
• Phase II only: Mesothelioma originating outside the pleura (e.g.: peritoneum)
• Absence of measurable lesions
• 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.
• 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)
• Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance
• Evidence of peripheral neuropathy \> grade 1 according to NCI-CTCAE Version 3
• Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to study entry
• Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception
• Known HIV, HBV, HCV infection
• Presence of CNS metastases

Sponsors & Collaborators

• CanBas Co. Ltd.: lead

Study Sites (12)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Arizona Cancer Center

Tucson, Arizona, 85719-1454, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Karmanos Cancer Institute/Wayne State University

Detroit, Michigan, 48201, United States

Location

Nevada Cancer Institute

Las Vegas, Nevada, 89135, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Memorial-Sloan Kettering Cancer Center

New York, New York, 10022, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Penn State Milton S. Hershey Medical Ctr.

Hershey, Pennsylvania, 17033, United States

Location

Cancer Therapy & Research Center

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (5)

• Suganuma M, Kawabe T, Hori H, Funabiki T, Okamoto T. Sensitization of cancer cells to DNA damage-induced cell death by specific cell cycle G2 checkpoint abrogation. Cancer Res. 1999 Dec 1;59(23):5887-91.

  PMID: 10606229 BACKGROUND

• 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.

  PMID: 17237275 BACKGROUND

• Mine N, Yamamoto S, Saito N, Yamazaki S, Suda C, Ishigaki M, Kufe DW, Von Hoff DD, Kawabe T. CBP501-calmodulin binding contributes to sensitizing tumor cells to cisplatin and bleomycin. Mol Cancer Ther. 2011 Oct;10(10):1929-38. doi: 10.1158/1535-7163.MCT-10-1139. Epub 2011 Aug 10.

  PMID: 21831962 BACKGROUND

• Shapiro GI, Tibes R, Gordon MS, Wong BY, Eder JP, Borad MJ, Mendelson DS, Vogelzang NJ, Bastos BR, Weiss GJ, Fernandez C, Sutherland W, Sato H, Pierceall WE, Weaver D, Slough S, Wasserman E, Kufe DW, Von Hoff D, Kawabe T, Sharma S. Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. Clin Cancer Res. 2011 May 15;17(10):3431-42. doi: 10.1158/1078-0432.CCR-10-2345. Epub 2011 Jan 10.

  PMID: 21220472 BACKGROUND

• 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.

  PMID: 22032894 BACKGROUND

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Pemetrexed; Cisplatin; Cdc25C phosphatase (211-221)

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Takumi Kawabe, MD, PhD
• Organization: CanBas Co., Ltd.

takumi@canbas.co.jp

81559543666

Study Officials

• Lee Krug

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2008
• First Posted: June 18, 2008
• Study Start: May 1, 2008
• Primary Completion: July 1, 2012
• Study Completion: November 1, 2012
• Last Updated: July 20, 2021
• Results First Posted: July 20, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)