NCT00700336 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2021-07-20

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
pemetrexed, cisplatin and CBP501
intervention Names
Drug: pemetrexed, cisplatin and CBP501
label
Pemetrexed, Cisplatin, and CBP501: Phase 2
type
EXPERIMENTAL
description
pemetrexed and cisplatin
intervention Names
Drug: pemetrexed and cisplatin
label
Pemetrexed and Cisplatin: Phase 2
type
ACTIVE_COMPARATOR
description
MTD, which was equal to recommended dose for the Phase II part, was determined by 6 patients (3+3)
intervention Names
Drug: pemetrexed, cisplatin and CBP501, dose finding
label
Pemetrexed, Cisplatin, and CBP501:Phase 1
type
EXPERIMENTAL

interventions

arm Group Labels
Pemetrexed, Cisplatin, and CBP501: Phase 2
description
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.
name
pemetrexed, cisplatin and CBP501
other Names
Arm A
type
DRUG
arm Group Labels
Pemetrexed and Cisplatin: Phase 2
description
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.
name
pemetrexed and cisplatin
other Names
Arm B
type
DRUG
arm Group Labels
Pemetrexed, Cisplatin, and CBP501:Phase 1
description
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.
name
pemetrexed, cisplatin and CBP501, dose finding
other Names
Phase I part
Dose finding
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 69
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
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

Full study description

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

Source references

references

citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
BACKGROUND

Source notices and limitations

Discovery and provenance

release id
ctgov-registry-1336d216cbd1bbff780dac70
edge id
nct-edge-4c613fd5e77c380fca7a
requested nct id
NCT00700336
primary nct id
NCT00700336
source kind
ctgov_condition_query
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Malignant+Mesothelioma&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true
source record id
Source null
source file sha256
0a018dbf1aa46f57978b6d16aa19b94d76d6d65cf1e297e889c8e599fef1fab1
payload sha256
a429becb0deb3e5548f853c5f830381b608802ceca87b9b7ec8a29ebdf03e6f1
payload
clinical indication matching status
condition_index_match_asserted_by_registry_not_reviewed
end exclusive
true
id
nct-edge-4c613fd5e77c380fca7a
link basis
returned_by_explicit_condition_and_posted_results_filter_query
nct id
NCT00700336
occurrences
context exact
NCT00700336
end
11
exact text
NCT00700336
start
0
offset unit
unicode_code_points
query cond
Malignant Mesothelioma
query disease state id
ds-malignant-mesothelioma
source file
/Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-malignant-mesothelioma-000.json
source file sha256
0a018dbf1aa46f57978b6d16aa19b94d76d6d65cf1e297e889c8e599fef1fab1
source json pointer
/studies/35/protocolSection/identificationModule/nctId
source kind
ctgov_condition_query
source record id
Source null
source string basis
parsed_JSON_string_unmodified
source string sha256
074b7365900f97cdba576b5a7130b96502238a13260c60c484f8d7891a106d61
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Malignant+Mesothelioma&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice