Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma

NCT ID: NCT01843374

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 571 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-17
• Study Completion Date: 2026-06-30

Brief Summary

This is a Phase 2b, randomized, double-blind, parallel-group study. Subjects with unresectable pleural or peritoneal malignant mesothelioma will be randomized in a 2:1 ratio to receive either tremelimumab or placebo. Approximately 564 subjects will be enrolled at study centers in multiple countries. The study consists of a screening period, a treatment period, a 90-day follow-up period for safety, and a long-term survival follow-up period.

Detailed Description

This is a Phase 2b, randomized, double-blind, parallel-group study. Subjects with unresectable pleural or peritoneal malignant mesothelioma will be randomized in a 2:1 ratio to receive either tremelimumab or placebo.

Randomization will be stratified by EORTC status (low-risk vs high-risk), line of therapy (second vs third), and anatomical site (pleural vs peritoneal). This study plans to use the EORTC to stratify subjects into high or low risk groups in order to ensure balanced randomization to the different treatment groups. For subjects in whom pemetrexed was contraindicated or not tolerated or not an approved therapy (eg, peritoneal mesothelioma), prior therapy with a first-line platinum-based regimen is required. Approximately 564 subjects will be enrolled at study centers in multiple countries.

The study consists of a screening period, a treatment period, a 90-day follow-up period for safety, and a long-term survival follow-up period.

Conditions

Unresectable Pleural or Peritoneal Malignant Mesothelioma

Keywords

tremelimumab; pleural, peritoneal; malignant mesothelioma; CTLA-4

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tremelimumab

Tremelimumab

Group Type: EXPERIMENTAL

Tremelimumab

Intervention Type: DRUG

Tremelimumab is to be administered as an IV solution, followed by observation.

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo is to be administered as an IV solution, followed by observation.

Interventions

Tremelimumab

Tremelimumab is to be administered as an IV solution, followed by observation.

Intervention Type: DRUG

Placebo

Placebo is to be administered as an IV solution, followed by observation.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically and/or cytologically confirmed pleural or peritoneal malignant mesothelioma;

2. Disease not amenable to curative surgery;

3. Age 18 and over at the time of consent;

4. ECOG Performance status 0-1;

5. Progressed after previous receipt of 1-2 prior systemic treatments for advanced disease that included a first-line pemetrexed (or anti-folate)-based regimen in combination with platinum agent.

6. Recovered from all toxicities associated with prior treatment, to acceptable baseline status, or a NCI CTCAE Grade of 0 or 1, except for toxicities not considered a safety risk,

7. Measurable diseaseby modified RECIST for pleural mesothelioma or RECIST v1.1 for peritoneal mesothelioma;

8. Adequate bone marrow, hepatic, and renal function determined within 14 days prior to randomization defined as:

9. Negative screening test results for human immunodeficiency virus (HIV), hepatitis A, B and C.

10. Written informed consent and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive authorization in the EU) obtained from the subject/legal representative prior to performing any protocol- related procedures, including screening evaluations;

11. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician.

12. Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Days 1 through 90 post last dose. In addition, they must refrain from sperm donation for 90 days after the final dose of investigational product.

Exclusion Criteria

1. Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma;

2. Received any prior mAb against CTLA-4, programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1);

3. History of chronic inflammatory or autoimmune disease with symptomatic disease within the last 3 years prior to randomization.

4. Active, untreated central nervous system (CNS) metastasis

5. Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product;

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

7. Pregnant or breast feeding at time of consent;

8. Any condition that would prohibit the understanding or rendering of information and consent and compliance with the requirements of this protocol;

9. Active or history of diverticulitis;

10. Active or history of inflammatory bowel disease, irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Active or history of systemic lupus erythematosus or granulomatosis with polyangiitis;

11. History of sarcoidosis syndrome;

12. Currently receiving systemic corticosteroids or other immunosuppressive medications or has a medical condition that requires the chronic use of corticosteroids.

13. Subjects should not be vaccinated with live attenuated vaccines within one month prior to starting tremelimumab treatment;

14. The last dose of prior chemotherapy or radiation therapy was received less than 2 weeks prior to randomization;

15. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of vitiligo and alopecia;

16. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results;

17. Concurrent enrollment in another clinical study or receipt of an investigational product within the last 4 weeks

18. Employees of the study site directly involved with the conduct of the study, or immediate family members of any such individuals;

19. Subjects with a history of hypersensitivity to compounds of similar biologic composition to tremelimumab or any constituent of the product.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Scottsdale, Arizona, United States

Research Site

La Jolla, California, United States

Research Site

Los Angeles, California, United States

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San Francisco, California, United States

Research Site

Santa Monica, California, United States

Research Site

New Haven, Connecticut, United States

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Newark, Delaware, United States

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Tampa, Florida, United States

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Augusta, Georgia, United States

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Chicago, Illinois, United States

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Peoria, Illinois, United States

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Baltimore, Maryland, United States

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Baltimore, Maryland, United States

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Minneapolis, Minnesota, United States

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New York, New York, United States

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Rochester, New York, United States

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Durham, North Carolina, United States

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Canton, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Adelaide, , Australia

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Auchenflower, , Australia

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Box Hill, , Australia

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Chermside, , Australia

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East Bentleigh, , Australia

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Gosford, , Australia

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Heidelberg, , Australia

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Nedlands, , Australia

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Saint Leonards, , Australia

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Waratah, , Australia

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Edegem, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Toronto, Ontario, Canada

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Sainte-Foy, Quebec, Canada

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Copenhagen, , Denmark

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Caen, , France

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Le Mans, , France

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Lille, , France

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Nice, , France

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Rennes, , France

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Toulouse, , France

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Villejuif, , France

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Berlin, , Germany

Research Site

Esslingen a.N., , Germany

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Freiburg im Breisgau, , Germany

Research Site

Gauting, , Germany

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Großhansdorf, , Germany

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Hamburg, , Germany

Research Site

Hemer, , Germany

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Karlsruhe, , Germany

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Löwenstein, , Germany

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Lübeck, , Germany

Research Site

Gyöngyös - Mátraháza, , Hungary

Research Site

Törökbálint, , Hungary

Research Site

Beersheba, , Israel

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Alessandria, , Italy

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Aviano, , Italy

Research Site

Bergamo, , Italy

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Bologna, , Italy

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Candiolo, , Italy

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Genova, , Italy

Research Site

Meldola, , Italy

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Milan, , Italy

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Orbassano, , Italy

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Padua, , Italy

Research Site

Rozzano, , Italy

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Siena, , Italy

Research Site

Breda, , Netherlands

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Eindhoven, , Netherlands

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Rotterdam, , Netherlands

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Gdansk, , Poland

Research Site

Poznan, , Poland

Research Site

Szczecin, , Poland

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Warsaw, , Poland

Research Site

Craiova, , Romania

Research Site

Moscow, , Russia

Research Site

Nizhny Novgorod, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Kraaifontein, , South Africa

Research Site

Pretoria, , South Africa

Research Site

Pretoria, , South Africa

Research Site

Jeonnam, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Barcelona, , Spain

Research Site

Donostia / San Sebastian, , Spain

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Madrid, , Spain

Research Site

Sabadell (Barcelona), , Spain

Research Site

Seville, , Spain

Research Site

Linköping, , Sweden

Research Site

Lund, , Sweden

Research Site

Umeå, , Sweden

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Leeds, , United Kingdom

Research Site

Leicester, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Maidstone, , United Kingdom

Research Site

Manchester, , United Kingdom

Research Site

Metropolitan Borough of Wirral, , United Kingdom

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Plymouth, , United Kingdom

Research Site

Southampton, , United Kingdom

Countries

Brazil; United States; Australia; Belgium; Canada; Denmark; France; Germany; Hungary; Israel; Italy; Netherlands; Poland; Romania; Russia; South Africa; South Korea; Spain; Sweden; United Kingdom

References

Baverel P, Roskos L, Tatipalli M, Lee N, Stockman P, Taboada M, Vicini P, Horgan K, Narwal R. Exposure-Response Analysis of Overall Survival for Tremelimumab in Unresectable Malignant Mesothelioma: The Confounding Effect of Disease Status. Clin Transl Sci. 2019 Sep;12(5):450-458. doi: 10.1111/cts.12633. Epub 2019 Apr 12.

Reference Type: DERIVED

PMID: 30883000 (View on PubMed)

Maio M, Scherpereel A, Calabro L, Aerts J, Perez SC, Bearz A, Nackaerts K, Fennell DA, Kowalski D, Tsao AS, Taylor P, Grosso F, Antonia SJ, Nowak AK, Taboada M, Puglisi M, Stockman PK, Kindler HL. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017 Sep;18(9):1261-1273. doi: 10.1016/S1470-2045(17)30446-1. Epub 2017 Jul 17.

Reference Type: DERIVED

PMID: 28729154 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=180&filename=FINAL%20Redacted%20PROTOCOL_%2003Jan2017.pdf

FINAL Redacted PROTOCOL\_ 03Jan2017

Other Identifiers

2012-003524-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D4880C00003

Identifier Type: -

Identifier Source: org_study_id