Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients

Mesothelioma Clinical Trial

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Official title:

A Phase III, Randomized, Open Label Trial of Nivolumab in Combination With Ipilimumab Versus Pemetrexed With Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02899299
• Other study ID #: CA209-743
• Secondary ID: 2016-001859-43
• Status: Completed
• Phase: Phase 3
• Start date: November 29, 2016
• Est. completion date: April 28, 2023

Study information

• Verified date: April 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the effectiveness and tolerability of the combination of Nivolumab and Ipilimumab compared to Pemetrexed and Cisplatin or Carboplatin in patients with unresectable pleural mesothelioma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 605
• Est. completion date: April 28, 2023
• Est. primary completion date: March 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Males and Females at least 18 years of age

• Histologically confirmed pleural malignant mesothelioma not eligible for curative surgery

• ECOG Performance status of 0 or 1

• Available tumor sample for testing

• Acceptable blood work

Exclusion Criteria:

• Primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas

• Prior chemotherapy for pleural mesothelioma

• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 oranti-CTLA-4 antibody

• History of other malignancy unless the subject has been disease-free for at least 3 years

• Active, untreated central nervous system (CNS) metastasis

Other protocol defined inclusion/exclusion criteria could apply

Related Conditions & MeSH terms

• Mesothelioma
• Mesothelioma, Malignant

Intervention

Biological:
• Nivolumab

• Ipilimumab

Drug:
• Pemetrexed

• Cisplatin

• Carboplatin

Locations

Country	Name	City	State
Australia	Local Institution - 0031	Birtinya	Queensland
Australia	Local Institution - 0033	Clayton	Victoria
Australia	Local Institution - 0030	Malvern	Victoria
Australia	Local Institution - 0034	Nedlands	Western Australia
Australia	Local Institution - 0032	Sydney	New South Wales
Belgium	Local Institution - 0089	Brussels
Belgium	Local Institution - 0086	Edegem
Belgium	Local Institution - 0087	Liège
Belgium	Local Institution - 0088	Sint-Niklaas
Brazil	Local Institution	Barretos	Sao Paulo
Brazil	Local Institution - 0064	Sao Paulo
Chile	Local Institution - 0018	Santiago	Metropolitana
China	Local Institution	Changchun	Jilin
China	Local Institution - 0133	Harbin Shi	Heilongjiang
China	Local Institution - 0124	Kunming
China	Local Institution - 0120	Shanghai
China	Local Institution	Shenyang	Liaoning
Colombia	Local Institution - 0039	Bogota
Colombia	Local Institution - 0040	Bogota
France	Local Institution - 0057	Caen
France	Local Institution - 0073	Creteil
France	Local Institution - 0074	La Tronche
France	Local Institution - 0067	Lille Cedex
France	Local Institution - 0069	Marseille Cedex 20
France	Local Institution - 0056	Paris
France	Local Institution - 0080	Saint Herblain
France	Local Institution - 0093	Strasbourg Cedex
France	Local Institution - 0058	Toulon Cedex
France	Local Institution - 0068	Toulouse Cedex 9
Germany	Local Institution - 0026	Cologne
Germany	Local Institution - 0054	Coswig
Germany	Local Institution - 0038	Essen
Germany	Local Institution - 0023	Gottingen
Germany	Local Institution - 0024	Grosshansdorf
Germany	Local Institution - 0027	Hamburg
Germany	Local Institution - 0037	Heidelberg
Germany	Local Institution - 0021	Homburg an d. Saar
Germany	Local Institution - 0022	Immenhausen
Germany	Local Institution - 0019	Moers
Greece	Local Institution - 0017	Athens
Greece	Local Institution - 0016	Thessaloniki
Italy	Local Institution - 0047	Aviano
Italy	Local Institution - 0044	Bari
Italy	Local Institution - 0046	Catania
Italy	Local Institution - 0045	Genova
Italy	Local Institution - 0043	Napoli
Italy	Local Institution - 0042	Ravenna	Emilia-Romagna
Italy	Local Institution - 0048	Rozzano
Italy	Local Institution - 0041	Siena
Japan	Local Institution - 0106	Amagasaki-shi	Hyogo
Japan	Local Institution - 0097	Chiba-shi	Chiba
Japan	Local Institution - 0094	Chuo-ku	Tokyo
Japan	Local Institution - 0108	Fukuyama-shi	Hiroshima
Japan	Local Institution - 0114	Hiroshima-Shi	Hiroshima
Japan	Local Institution - 0096	Kitaadachi-gun	Saitama
Japan	Local Institution - 0105	Nagoya-shi	Aichi
Japan	Local Institution - 0104	Natori-shi	Miyagi
Japan	Local Institution - 0107	Niigata-shi	Niigata
Japan	Local Institution - 0098	Nishinomiya-shi	Hyogo
Japan	Local Institution - 0100	Okayama-shi	Okayama
Japan	Local Institution - 0113	Osakasayama-city
Japan	Local Institution - 0101	Sapporo-shi	Hokkaido
Japan	Local Institution - 0099	Ube-shi	Yamaguchi
Japan	Local Institution - 0095	Yokohama-shi	Kanagawa
Mexico	Local Institution - 0118	Chihuahua
Mexico	Local Institution - 0079	Df	Distrito Federal
Mexico	Local Institution - 0051	Guadalajara	Jalisco
Mexico	Local Institution - 0050	Mexico	Distrito Federal
Mexico	Local Institution - 0053	Mexico	Distrito Federal
Netherlands	Local Institution - 0092	Amsterdam
Netherlands	Local Institution - 0091	Rotterdam
Poland	Local Institution - 0078	Bytom
Poland	Local Institution - 0076	Krakow
Poland	Local Institution - 0077	Warszawa
Romania	Local Institution - 0115	Bucharest
Romania	Local Institution - 0109	Bucuresti
Romania	Local Institution - 0102	Craiova
Romania	Local Institution - 0055	Romania
Russian Federation	Local Institution - 0071	Moscow
Russian Federation	Local Institution - 0150	Moscow
Russian Federation	Local Institution - 0072	Saint Petersburg
South Africa	Local Institution - 0059	Cape Town	Western Cape
South Africa	Local Institution - 0060	Pretoria	Gauteng
Switzerland	Local Institution - 0049	Bern
Switzerland	Local Institution - 0036	Lausanne
Switzerland	Local Institution - 0029	Zurich
Turkey	Local Institution - 0111	Diyarbakir
Turkey	Local Institution - 0112	Istanbul
Turkey	Local Institution - 0110	Seyhan
United Kingdom	Local Institution - 0084	Edinburgh	Midlothian
United Kingdom	Local Institution - 0081	Leicester
United Kingdom	Local Institution - 0083	London
United Kingdom	Local Institution - 0116	Manchester
United Kingdom	Local Institution - 0090	Southampton
United Kingdom	Local Institution - 0085	Truro	Cornwall
United States	Univ Of Maryland Greenbaum Cancer Center	Baltimore	Maryland
United States	Local Institution - 0002	Chicago	Illinois
United States	Local Institution - 0007	Cleveland	Ohio
United States	Local Institution - 0013	Detroit	Michigan
United States	Cancer & Hematology Centers Of Western Michigan	Grand Rapids	Michigan
United States	Local Institution - 0005	Houston	Texas
United States	West Virginia University	Morgantown	West Virginia
United States	Local Institution - 0014	New Haven	Connecticut
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny Cancer Center	Pittsburgh	Pennsylvania
United States	Local Institution - 0004	Rochester	Minnesota
United States	Ucsf	San Francisco	California
United States	H. Lee Moffitt Cancer Center & Research Inst, Inc	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Chile,  China,  Colombia,  France,  Germany,  Greece,  Italy,  Japan,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  South Africa,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall Survival was defined as the time from randomization to the date of death due to any cause. A participant who has not died was censored at last known date alive.	From randomization to the date of death (Up to 40 Months)
Secondary	Objective Response Rate (ORR)	Objective Response Rate is defined as the percentage of randomized participants who achieve a best overall response of complete response (CR) or partial response (PR) per Blinded Independent Central Review (BICR) assessments. Per adapted m-RECIST for pleural mesothelioma, each single tumor measurement must be at least 10 mm in length to qualify as measureable disease and contribute to the sum that defines the pleural uni-variate measure. Per RECIST 1.1 for solid tumors, confirmation of response required: CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the Total Tumor Measurement; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (Up to 76 months)
Secondary	Disease Control Rate (DCR)	Disease Control Rate is defined as the percentage of all randomized participants whose Best Overall Response was complete response (CR), partial response (PR), stable disease (SD) or Non-CR/Non-PD as assessed by Blinded Independent Central Review (BICR). Per adapted m-RECIST for pleural mesothelioma, each single tumor measurement must be at least 10 mm in length to qualify as measureable disease and contribute to the sum that defines the pleural uni-variate measure. Per RECIST 1.1 for solid tumors, confirmation of response required: CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the Total Tumor Measurement; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement; SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Non-CR/Non-PD: Persistence of one or more non-target lesion(s).	From randomization date to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (Up to 76 months
Secondary	Progression Free Survival (PFS)	Progression Free Survival is defined as the time between the date of randomization and the date of first documented tumor progression per Blinded Independent Central Review (BICR) assessments (using adapted m-RECIST and RECIST 1.1), or death due to any cause, whichever occurs first. Participants who received subsequent anticancer therapy prior to documented progression were censored at the date of the last evaluable tumor assessment conducted on or prior to the date of initiation of the subsequent anticancer therapy.; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of first documented tumor progression or death due to any cause, whichever occurs first. (up to 76 months)
Secondary	Overall Survival (OS) According to PD-L1 Expression Level	PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by overall survival (OS) analysis. OS was defined as the time from randomization to the date of death due to any cause. A participant who has not died was censored at last known date alive.	From randomization date to the date of death (Up to 76 Months)
Secondary	Progression Free Survival (PFS) According to PD-L1 Expression Level	PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by progression free survival (PFS) analysis. PFS is defined as the time between the date of randomization and the date of first documented tumor progression per Blinded Independent Central Review (BICR) assessments (using adapted m-RECIST and RECIST 1.1), or death due to any cause, whichever occurs first. Participants who received subsequent anticancer therapy prior to documented progression were censored at the date of the last evaluable tumor assessment conducted on or prior to the date of initiation of the subsequent anticancer therapy.; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of first documented tumor progression or death due to any cause, whichever occurs first. (up to 76 months)
Secondary	Objective Response Rate (ORR) According to PD-L1 Expression Level	PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by objective response rate (ORR) analysis. ORR is defined as the percentage of participants who achieve a best overall response of complete response (CR) or partial response (PR) per Blinded Independent Central Review (BICR) assessments. Per adapted m-RECIST for pleural mesothelioma, each single tumor measurement must be at least 10 mm in length to qualify as measureable disease and contribute to the sum that defines the pleural uni-variate measure.; per RECIST 1.1 for solid tumors, confirmation of response required: CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the Total Tumor Measurement; Progressive disease (PD)=At least a 20% increase in the sum of the Total Tumor Measurement.	From randomization date to the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first (Up to 76 months)

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting