Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Pemetrexed

Cisplatin

Pevonedistat

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.

pevonedistat

Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.

Pemetrexed and cisplatin

Majorie Zauderer, MD

The purpose of this study is to test any good and bad effects of activity pevonedistat taken alone, and also to test the safety of pevonedistat in combination with standard chemotherapy, pemetrexed/cisplatin.

This study is a single institution trial with two cohorts to test the efficacy of the NEDD8 inhibitor, pevonedistat as a single agent in patients with NF2 mutant MM (Cohort 1), and also to test the safety of pevonedistat in combination with standard chemotherapy, pemetrexed/cisplatin (Cohort 2).

Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma

Pevonedistat as a Single Agent and in Combination With Chemotherapy in Patients With Malignant Mesothelioma

The CBR is defined as the proportion of patients CR, PR or SD at 18 weeks based on RECIST criteria.

If none of the initial cohort of 3 has a dose-limited toxicity the dose level will be escalated. If one has a DLT that dose level will be expanded with 3 more patients. Dose escalation will stop if ≥2 DLTs are seen at a dose level. The MTD is defined as the highest dose level at which no more than 1 of the 6 patients at that level has a DLT. If no patient in the 3-patient cohort has a DLT and the dose level is under final consideration of the MTD, an additional three patients will be treated at that level for confirmation.

M.D. Anderson Cancer Center

Memorial Sloan Kettering Cancer Center

No participants accrued to Pevonedistat in Combination With Pemetrexed and Cisplatin cohort

pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.

pevonedistat: Pevonedistat will be administered as an IV infusion at a dose of 50 mg/m2 days 1, 3, and 5 of a 21-day cycle.Treatment will be administered as an outpatient.

Pemetrexed and cisplatin: Pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2, will be given at fixed doses on day 1 of each cycle.

Pevonedistat in Combination With Pemetrexed and Cisplatin

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

No participants accrued to pevonedistat in combination with pemetrexed and cisplatin cohort

Dr. Marjorie Zauderer, MD

Number of Patients Who Have a Clinical Benefit Rate (CBR) (Cohort 1)

Maximum Tolerated Dose (MTD) (Cohort 2)

Overall Study

Pharmaceutical Solutions

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

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, cisplatin and CBP501

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 and cisplatin

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.

pemetrexed, cisplatin and CBP501, dose finding

Lee Krug

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.

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

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

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

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.

CanBas Co. Ltd.

pemetrexed, cisplatin and CBP501

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.

Pemetrexed, Cisplatin, and CBP501: Phase 2

pemetrexed and cisplatin

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.

Pemetrexed and Cisplatin: Phase 2

DL1: CBP501 16mg/m2, Alimta 500mg/m2, cisplatin 75mg/m2 DL2: CBP501 25mg/m2, Alimta 500mg/m2, cisplatin 75mg/m2

Pemetrexed, Cisplatin, and CBP501: Phase 1

Takumi Kawabe, MD, PhD

4M PFS by Independent Image Review

4M PFS by Site assess

Pemetrexed, Cisplatin, and CBP501 administered once every 3 weeks

Pemetrexed, Cisplatin, and CBP501

Pemetrexed and Cisplatin every three weeks

Pemetrexed and Cisplatin

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

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.

Pemetrexed, Cisplatin and CBP501: Phase 2

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.

DL1: CBP501 16mg/m2, pemetrexed 500mg/m2, cisplatin 75mg/m2 DL2: CBP501 25mg/m2, pemetrexed 500mg/m2, cisplatin 75mg/m2

Pemetrexed, Cisplatin and CBP501: Phase 1

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Investigational treatment (pazopanib and pemetrexed)

Standard treatment (pemetrexed and cisplatin)

oral pazopanib 600 mg once daily and pemetrexed intravenous (IV) 500mg/m\^2 once every 3 weeks, then pazopanib 800 mg once daily

pazopanib and pemetrexed

pemetrexed IV 500 mg/m\^2 and cisplatin IV 75 mg/m\^2 once every 3 weeks

GSK Clinical Trials

The main purpose of this study is to determine whether the combination of pazopanib and pemetrexed is safe and effective in the treatment of advanced non-small cell lung cancer (NSCLC).

Study of Pazopanib and Pemetrexed in Advanced Non-small Cell Lung Cancer

An Open-label, Multicentre, Randomised Phase II Study of Pazopanib in Combination With Pemetrexed in First-line Treatment of Subjects With Predominantly Non-squamous Cell Stage IIIBwet/IV Non-small Cell Lung Cancer

PFS is defined as the interval between the date of randomization (date on which the investigator evaluated the participant and first determined he/she had disease progression) and the first occurrence of progressive disease (PD) or death from any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1, PD is defined as a \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of \>=1 new lesion).

OS was determined from the date of randomization to the date of death from any cause. Participants who had not died at the time of the cut-off for the final analysis were censored at the date the participants were last known to be alive. Because enrollment in the study was halted prematurely, the ability to achieve an estimate of OS was compromised. Consequently, OS was not estimated.

Tumor response was assessed by the Investigator according to the RECIST, version 1.0. A participant was defined as a responder if he/she sustained a complete response (CR; the disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions) for at least 4 weeks at any time during randomized treatment. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.

The percentage of participants with a complete response or a partial response was evaluated.

GlaxoSmithKline

Serious adverse events (SAEs) and non-serious AEs are presented for the entire treatment period (Combination Treatment Phase followed by the Monotherapy Phase). SAEs and AEs were collected in the Safety Population, comprised all participants who had received at least one dose of both drugs within the assigned regimen.

Oral pazopanib 600 milligrams (mg) once daily plus intravenous pemetrexed 500 mg/meters squared (m\^2) once every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase.

Pazopanib 600 mg Plus Pemetrexed 500 mg/m^2

Oral pazopanib 800 mg once daily plus intravenous (IV) pemetrexed 500 mg/ m\^2 once every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase. If participants experienced no disease progression, unacceptable toxicities, or death during the Combination Treatment Phase, they continued on pazopanib 800 mg monotherapy until disease progression, unacceptable toxicities, or death.

Pazopanib 800 mg Plus Pemetrexed 500 mg/m^2

IV cisplatin 75 mg/m\^2 plus intravenous pemetrexed 500 mg/m\^2 once daily every 3 weeks for 4 or 6 cycles during the Combination Treatment Phase. Until Protocol Amendment 2, upon disease progression participants had the opportunity to receive pazopanib 800 mg monotherapy if the investigator considered it an appropriate treatment option after considering alternative options for second-line treatment.

Cisplatin 75 mg/m^2 Plus Pemetrexed 500 mg/m^2

Age Continuous

African American/African Heritage

Asian - Central/South Asian Heritage

White - Arabic/North African Heritage

White - White/Caucasian/European Heritage

Race/Ethnicity, Customized

Efficacy data were only summarized for the pazopanib (pazo.) 800 mg + pemetrexed (peme.) 500 mg/m\^2 and the cisplatin 75 mg/m\^2 + peme. 500 mg/m\^2 arms due to the small sample size/short treatment duration in the pazo. 600 mg + peme. 500 mg/m\^2 arm.

GSK Response Center

Intent-to-Treat (ITT) Population: all participants randomized to receive treatment and who were analyzed based on the assigned randomized treatment and not based on actual treatment received/not received. Participants who had neither progressed nor died were censored at the date of the last adequate tumor assessment at the time of the cut-off.

Progression-free Survival (PFS)

Overall Survival (OS)

Complete response

Partial response

Stable disease

Progressive disease

Unknown

ITT Population. A participant without a post-baseline assessment of response was considered to be a non-responder; i.e., all randomized participants are included in the denominator.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma	NCT03319537	Mesothelioma	pevonedistat Pemetrexed and ...	18 Years -	Memorial Sloan Kettering Cancer Center
Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II)	NCT00700336	Malignant Pleur... Solid Tumors	pemetrexed, cis... pemetrexed and ... pemetrexed, cis...	18 Years -	CanBas Co. Ltd.
Study of Pazopanib and Pemetrexed in Advanced Non-small Cell Lung Cancer	NCT00871403	Lung Cancer, No...	pazopanib and p... pemetrexed and ...	18 Years -	GlaxoSmithKline
Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II)	NCT00700336	Malignant Pleur... Solid Tumors	pemetrexed, cis... pemetrexed and ... pemetrexed, cis...	18 Years -	CanBas Co. Ltd.

Spots Global Cancer Trial Database for pemetrexed and cisplatin