Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma
Tremelimumab
A Phase 2b, Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Second- or Third-line Treatment of Subjects With Unresectable Pleural or Peritoneal Malignant Mesothelioma
2 other identifiers
interventional
571
19 countries
104
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2013
Longer than P75 for phase_2
104 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 22, 2013
CompletedFirst Posted
Study publicly available on registry
April 30, 2013
CompletedStudy Start
First participant enrolled
May 17, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 24, 2016
CompletedResults Posted
Study results publicly available
August 17, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 31, 2027
ExpectedJuly 27, 2026
June 1, 2026
2.7 years
April 22, 2013
April 10, 2017
July 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
Overall survival (OS) by treatment arm
3 years.
Secondary Outcomes (9)
OS Rate at 18 Months by Treatment Arm
18 months
Progression-free Survival by Treatment Arm
Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.
Overall Response Rate by Treatment Arm
Time from randomization to best response to treatment, assessed up to 3 years.
Duration of Response by Treatment Arm
Duration of response from the first documentation of objcetive response (confirmed CR or PR) to the first documented disease progression, assessed up to 14 weeks after the initial response.
Disease Control Rate by Treatment Arm
Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.
- +4 more secondary outcomes
Study Arms (2)
Tremelimumab
EXPERIMENTALTremelimumab
Placebo
PLACEBO COMPARATORPlacebo
Interventions
Tremelimumab is to be administered as an IV solution, followed by observation.
Eligibility Criteria
You may qualify if:
- Histologically and/or cytologically confirmed pleural or peritoneal malignant mesothelioma;
- Disease not amenable to curative surgery;
- Age 18 and over at the time of consent;
- ECOG Performance status 0-1;
- 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.
- 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,
- Measurable diseaseby modified RECIST for pleural mesothelioma or RECIST v1.1 for peritoneal mesothelioma;
- Adequate bone marrow, hepatic, and renal function determined within 14 days prior to randomization defined as:
- Negative screening test results for human immunodeficiency virus (HIV), hepatitis A, B and C.
- 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;
- 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.
- 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.
You may not qualify if:
- Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma;
- Received any prior mAb against CTLA-4, programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1);
- History of chronic inflammatory or autoimmune disease with symptomatic disease within the last 3 years prior to randomization.
- Active, untreated central nervous system (CNS) metastasis
- Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product;
- History of other malignancy unless the subject has been disease-free for at least 3 years;
- Pregnant or breast feeding at time of consent;
- Any condition that would prohibit the understanding or rendering of information and consent and compliance with the requirements of this protocol;
- Active or history of diverticulitis;
- 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;
- History of sarcoidosis syndrome;
- Currently receiving systemic corticosteroids or other immunosuppressive medications or has a medical condition that requires the chronic use of corticosteroids.
- Subjects should not be vaccinated with live attenuated vaccines within one month prior to starting tremelimumab treatment;
- The last dose of prior chemotherapy or radiation therapy was received less than 2 weeks prior to randomization;
- Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of vitiligo and alopecia;
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- MedImmune LLClead
Study Sites (104)
Research Site
Scottsdale, Arizona, 85259, United States
Research Site
La Jolla, California, 92093, United States
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Los Angeles, California, 90025, United States
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San Francisco, California, 94143, United States
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Santa Monica, California, 90404, United States
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New Haven, Connecticut, 06511, United States
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Newark, Delaware, 19718, United States
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Tampa, Florida, 33612, United States
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Augusta, Georgia, 30912, United States
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Chicago, Illinois, 60637, United States
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Peoria, Illinois, 61615, United States
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Baltimore, Maryland, 21201, United States
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Baltimore, Maryland, 21231, United States
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Minneapolis, Minnesota, 55445, United States
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New York, New York, 10065, United States
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Rochester, New York, 14642, United States
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Durham, North Carolina, 27710, United States
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Canton, Ohio, 44710, United States
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Philadelphia, Pennsylvania, 19104, United States
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Dallas, Texas, 75390, United States
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Houston, Texas, 77030, United States
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Adelaide, 5000, Australia
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Auchenflower, 4066, Australia
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Box Hill, 3128, Australia
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Chermside, 4032, Australia
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East Bentleigh, 3165, Australia
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Gosford, 2250, Australia
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Heidelberg, 3084, Australia
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Nedlands, 6009, Australia
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Saint Leonards, 2065, Australia
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Waratah, 2298, Australia
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Edegem, 2650, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Toronto, Ontario, M5G 2M9, Canada
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Sainte-Foy, Quebec, G1V 4G5, Canada
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Copenhagen, 2100, Denmark
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Caen, 14076, France
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Le Mans, 72037, France
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Lille, 59037, France
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Nice, 06189, France
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Rennes, 35033, France
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Toulouse, 31059, France
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Villejuif, 94805, France
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Berlin, 13125, Germany
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Esslingen a.N., 73730, Germany
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Freiburg im Breisgau, 79106, Germany
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Gauting, 82131, Germany
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Großhansdorf, 22927, Germany
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Hamburg, 21075, Germany
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Hemer, 58675, Germany
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Karlsruhe, 76137, Germany
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Löwenstein, 74245, Germany
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Lübeck, 23538, Germany
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Gyöngyös - Mátraháza, 3200, Hungary
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Törökbálint, 2045, Hungary
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Beersheba, 84101, Israel
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Alessandria, 15100, Italy
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Aviano, 33081, Italy
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Bergamo, 24125, Italy
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Bologna, 40138, Italy
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Candiolo, 10060, Italy
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Genova, 16132, Italy
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Meldola, 47014, Italy
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Milan, 20133, Italy
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Orbassano, 10043, Italy
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Padova, 35128, Italy
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Rozzano, 20089, Italy
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Siena, 53100, Italy
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Breda, 4818 CK, Netherlands
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Eindhoven, 5623EJ, Netherlands
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Rotterdam, 3015 GD, Netherlands
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Gdansk, 80-952, Poland
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Poznan, 60-693, Poland
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Szczecin, 70-891, Poland
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Warsaw, 02-781, Poland
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Craiova, 200385, Romania
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Moscow, 115478, Russia
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Nizhny Novgorod, 603006, Russia
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Saint Petersburg, 197022, Russia
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Kraaifontein, 7570, South Africa
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Pretoria, 0081, South Africa
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Pretoria, 0181, South Africa
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Jeonnam, 58128, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Barcelona, 08035, Spain
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Donostia / San Sebastian, 20014, Spain
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Madrid, 28040, Spain
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Sabadell (Barcelona), 08208, Spain
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Seville, 41013, Spain
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Linköping, 58185, Sweden
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Lund, 22185, Sweden
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Umeå, SE90185, Sweden
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Leeds, LS9 7TF, United Kingdom
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Leicester, LE1 5WW, United Kingdom
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London, EC1A 7BE, United Kingdom
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London, SE1 9RT, United Kingdom
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Maidstone, ME16 9QQ, United Kingdom
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Manchester, M23 9LT, United Kingdom
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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
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Plymouth, PL6 8DH, United Kingdom
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Southampton, SO16 6YD, United Kingdom
Related Publications (2)
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.
PMID: 30883000DERIVEDMaio 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.
PMID: 28729154DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Baseline characteristics and efficacy outcomes are from the primary analysis reported in the main CSR based on a DCO of 24th January 2016. Participant flow and AE results are from the CSR Addendum based on a DBL of 23 January 2017.
Results Point of Contact
- Title
- Paul Stockman, MD, PhD
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 22, 2013
First Posted
April 30, 2013
Study Start
May 17, 2013
Primary Completion
January 24, 2016
Study Completion (Estimated)
May 31, 2027
Last Updated
July 27, 2026
Results First Posted
August 17, 2017
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure