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
- Conditions
- inoperabel maligne mesothelioomPleural or Peritoneal Mesothelioma
- Registration Number
- NL-OMON41613
- Lead Sponsor
- Medimmune LLC, subsidiary of AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 32
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 receipt of 1-2 prior systemic treatments for advanced disease that include a first-line pemetrexed (or anti-folate)-based regimen in combination with 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.
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;
- Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product, such as conditions associated with frequent diarrhea
- 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 NCI CTCAE Grade >- 2from previous anticancer therapy, with the exception of vitiligo and alopecia;
- 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.
- Subjects with a history of hypersensitivity to compounds of similar biologic composition to tremelimumab or any constituent of the product.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is OS which is defined as the time from randomization<br /><br>until death due to any cause.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary efficacy endpoints include OS rate at 18 months, durable DCR,<br /><br>PFS, PROs, ORR, and duration of response, based on modified Response Evaluation<br /><br>Criteria in Solid Tumors (RECIST) for pleural mesothelioma and RECIST criteria<br /><br>v1.1 for peritoneal mesothelioma.<br /><br><br /><br>The safety endpoints include adverse events (AEs) and serious adverse events<br /><br>(SAEs) changes from baseline in clinical laboratory evaluations,<br /><br>electrocardiograms (ECGs), and vital signs. Adverse events and SAEs will be<br /><br>assessed for severity and relationship to investigational product.<br /><br>The immunogenic potential of tremelimumab will be analyzed and the<br /><br>pharmacokinetics of tremelimumab will be assessed.</p><br>