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

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

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-003524-21-BE

Enrollment

564

Registered

2013-06-27

Start date

2013-08-13

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

unresectable pleural or peritoneal malignant mesothelioma MedDRA version: 18.0 Level: LLT Classification code 10034670 Term: Peritoneal mesothelioma malignant localised System Organ Class: 100000004864 MedDRA version: 18.0 Level: LLT Classification code 10035606 Term: Pleural mesothelioma malignant localised System Organ Class: 1000000

Interventions

Product Name: Tremelimumab Product Code: MEDI1123 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Tremelimumab

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Subjects must meet all of the following criteria: - 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 a platinum agent; - Recovered from all toxicities associated with prior treatment - Measurable disease - Adequate bone marrow, hepatic, and renal function - 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; - Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through 90 post last dose. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 188 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 376

Exclusion criteria

Exclusion criteria: Any of the following would exclude the subject from participation in the study: - Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma - Received any prior monoclonal antibody against CTLA-4, programmed cell death 1 (PD1) or programmed cell death 1 ligand 1 (PD-L1); - History of chronic inflammatory or autoimmune disease; - Active, untreated central nervous system (CNS) metastasis; - History of other malignancy unless the subject has been disease-free for at least 3 years. Non-invasive cancer history (such as carcinoma in situ [CIS] that has been resected) is allowed; - 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. Note that diverticulosis is permitted; - Active or history of inflammatory bowel disease (eg, colitis, Crohn's), irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Active or history of systemic lupus erythematosis or Wegener's granulomatosis; - History of sarcoidosis syndrome; - Currently receiving systemic corticosteroids or other immunosuppressive medications; - 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 (with the exception of palliative radiotherapy) was received less than 2 weeks prior to randomization; - Any unresolved toxicity from previous anticancer therapy; - 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; - Concurrent enrollment in another clinical study or receipt of an investigational product within the last 4 weeks (participation in the survival follow-up period of a study is not an exclusion criterion); - Employees of the study site directly involved with the conduct of the study, or immediate family members of any such individuals.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective is to compare the overall survival (OS) between the 2 treatment arms (tremelimumab and placebo) in subjects with unresectable malignant mesothelioma.; Secondary Objective: Secondary objectives are: - to estimate and compare OS rate at 18 months between the 2 treatment arms - to estimate and compare durable disease-control rate (DCR), progression-free survival (PFS), overall response rate (ORR) and duration of response between the two treatment arms - to evaluate the effect of tremelimumab on patient-reported outcomes (PROs), - to describe the safety and tolerability of tremelimumab in treated subjects, - to evaluate the immunogenicity of tremelimumab - and to describe the pharmacokinetics (PK) of tremelimumab in treated subjects. ;Primary end point(s): The primary endpoint is OS which is defined as the time from randomization until death due to any cause.;Timepoint(s) of evaluation of this end point: The primary endpoint is OS which is defined as the time from randomization until death due to any cause. For subjects who are alive at the time of data cutoff for the primary analysis or lost to follow-up, OS will be censored on the last date when subjects are known to be alive.	—

Measure

Time frame

Main Objective: The primary objective is to compare the overall survival (OS) between the 2 treatment arms (tremelimumab and placebo) in subjects with unresectable malignant mesothelioma.; Secondary Objective: Secondary objectives are: - to estimate and compare OS rate at 18 months between the 2 treatment arms - to estimate and compare durable disease-control rate (DCR), progression-free survival (PFS), overall response rate (ORR) and duration of response between the two treatment arms - to evaluate the effect of tremelimumab on patient-reported outcomes (PROs), - to describe the safety and tolerability of tremelimumab in treated subjects, - to evaluate the immunogenicity of tremelimumab - and to describe the pharmacokinetics (PK) of tremelimumab in treated subjects. ;Primary end point(s): The primary endpoint is OS which is defined as the time from randomization until death due to any cause.;Timepoint(s) of evaluation of this end point: The primary endpoint is OS which is defined as the time from randomization until death due to any cause. For subjects who are alive at the time of data cutoff for the primary analysis or lost to follow-up, OS will be censored on the last date when subjects are known to be alive.

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Secondary

Measure	Time frame
Secondary end point(s): The secondary efficacy endpoints include OS rate at 18 months, PRO as well as durable DCR, PFS, ORR, and duration of response, based on modified Response Evaluation Criteria in Solid Tumors (RECIST) for pleural mesothelioma and RECIST criteria v1.1 for peritoneal mesothelioma. The safety endpoints include adverse events (AEs) and serious adverse events (SAEs), changes from baseline in clinical laboratory evaluations, electrocardiograms (ECGs), and vital signs. Adverse events and SAEs will be assessed for severity and relationship to investigational product. The immunogenic potential of tremelimumab will be analyzed and the pharmacokinetics of tremelimumab will be assessed. ;Timepoint(s) of evaluation of this end point: The analysis of these secondary endpoints will be based on investigator-determined response data	—

Measure

Time frame

Secondary end point(s): The secondary efficacy endpoints include OS rate at 18 months, PRO as well as durable DCR, PFS, ORR, and duration of response, based on modified Response Evaluation Criteria in Solid Tumors (RECIST) for pleural mesothelioma and RECIST criteria v1.1 for peritoneal mesothelioma. The safety endpoints include adverse events (AEs) and serious adverse events (SAEs), changes from baseline in clinical laboratory evaluations, electrocardiograms (ECGs), and vital signs. Adverse events and SAEs will be assessed for severity and relationship to investigational product. The immunogenic potential of tremelimumab will be analyzed and the pharmacokinetics of tremelimumab will be assessed. ;Timepoint(s) of evaluation of this end point: The analysis of these secondary endpoints will be based on investigator-determined response data

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Countries

Australia, Belgium, Brazil, Canada, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, South Africa, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

Public ContactClinical Trial Enquiries

MedImmune, LLC

clinicaltrialenquiries@medimmune.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026