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Malignant Pleural MesotheliomaPhase 1/2NCT00700336

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

A Phase 1/2 study testing pemetrexed, cisplatin and CBP501, pemetrexed and cisplatin and pemetrexed, cisplatin and CBP501, dose finding in people with Malignant Pleural Mesothelioma and Solid Tumors, run by CanBas Co. Ltd. at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Pleural Mesothelioma, Solid Tumors
What is being tested?
pemetrexed, cisplatin and CBP501, pemetrexed and cisplatin and pemetrexed, cisplatin and CBP501, dose finding
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
12 sitesUnited States
Study dates
May 2008to Nov 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87131

  • University of Chicago

    Chicago, Illinois, 60637

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Karmanos Cancer Institute/Wayne State University

    Detroit, Michigan, 48201

  • City of Hope

    Duarte, California, 91010

  • Penn State Milton S. Hershey Medical Ctr.

    Hershey, Pennsylvania, 17033

  • Nevada Cancer Institute

    Las Vegas, Nevada, 89135

  • Memorial-Sloan Kettering Cancer Center

    New York, New York, 10022

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Cancer Therapy & Research Center

    San Antonio, Texas, 78229

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • Arizona Cancer Center

    Tucson, Arizona, 85719-1454

Other trials in United States

About this study

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

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.

Read the 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
Being tested
pemetrexed, cisplatin and CBP501, pemetrexed and cisplatin, pemetrexed, cisplatin and CBP501, dose finding
Keywords
malignant pleural mesothelioma, solid tumors
Medical subject headings
Mesothelioma, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pemetrexed, cisplatin and CBP501Drug

    Also called Arm A

    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 cisplatinDrug

    Also called Arm B

    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, dose findingDrug

    Also called Phase I part, 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.

Study groups in NCT00700336
Study groupRoleWhat they receive
Pemetrexed, Cisplatin, and CBP501: Phase 2Experimentalpemetrexed, cisplatin and CBP501
Receives: Drug: pemetrexed, cisplatin and CBP501
Pemetrexed and Cisplatin: Phase 2Active comparatorpemetrexed and cisplatin
Receives: Drug: pemetrexed and cisplatin
Pemetrexed, Cisplatin, and CBP501:Phase 1ExperimentalMTD, which was equal to recommended dose for the Phase II part, was determined by 6 patients (3+3)
Receives: Drug: pemetrexed, cisplatin and CBP501, dose finding

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: End of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionJul 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00700336
Sponsor's protocol ID
CBP08-01
Status last verified
Jun 2021
First submitted
16 Jun 2008
Last updated
20 Jul 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 10606229

  • 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.

    PubMed 17237275

  • 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.

    PubMed 21831962

  • 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.

    PubMed 21220472

  • 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.

    PubMed 22032894

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing pemetrexed, cisplatin and CBP501, pemetrexed and cisplatin and pemetrexed, cisplatin and CBP501, dose finding in people with Malignant Pleural Mesothelioma and Solid Tumors, run by CanBas Co. Ltd. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

4M PFS Rate of Patients With Previously Untreated, Unresectable Malignant Pleural Mesothelioma (MPM) Treated With CBP501, Pemetrexed and Cisplatin (time frame: End of study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00700336, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2021.

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