Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma
Condition: Unresectable Pleural or Peritoneal Malignant Mesothelioma
MeSH terms: Mesothelioma; Mesothelioma, Malignant; Lung Neoplasms
Intervention: Tremelimumab; Placebo
Intervention description: Tremelimumab is to be administered as an IV solution, followed by observation.; Placebo is to be administered as an IV solution, followed by observation.
Intervention MeSH terms: Tremelimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 571.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: tremelimumab; pleural, peritoneal; malignant mesothelioma; CTLA-4

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.
    

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.