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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01843374
First received: April 22, 2013
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Unresectable Pleural or Peritoneal Malignant Mesothelioma
Drug: Tremelimumab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Overall survival (OS) time by treatment arm [ Time Frame: Time from randomization until death due to any cause, assessed up to 3 years. ] [ Designated as safety issue: No ]
    The primary analysis of OS is defined as the time from randomization until death due to any cause.


Secondary Outcome Measures:
  • Durable disease control rate by treatment arm [ Time Frame: Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years. ] [ Designated as safety issue: No ]
    Durable DCR is defined as the proportion of participants with best response of complete response (CR), partial response (PR), or stable disease (SD) of ≥ 6 months duration

  • Length of progression-free survival by treatment arm [ Time Frame: Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years. ] [ Designated as safety issue: No ]
    Progression-free survival will be measured from randomization to the first documentation of disease progression or death due to any cause, whichever occurs first.

  • Overall response rate by treatment arm [ Time Frame: Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years. ] [ Designated as safety issue: No ]
    Overall response rate is defined as the proportion of participants with confirmed CR or PR.

  • Duration of response by treatment arm [ Time Frame: Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years. ] [ Designated as safety issue: No ]
    Duration of response will be defined as the duration from the first documentation of objective response (CR or PR) to the first documented disease progression.

  • Number of participants reporting any adverse event [ Time Frame: Day 1- 90 days post dose ] [ Designated as safety issue: Yes ]
    Any untoward medical occurrence in a patient or clinical investigation participants administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

  • Number of participants with changes in patient-reported outcomes [ Time Frame: Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years. ] [ Designated as safety issue: No ]
    Patient-reported outcomes as measured by the LCSS-Meso (for disease-related symptoms and health-related QoL), EQ-5D-3L (for health status), and BPI-sf (for pain) will be summarized descriptively; the change from baseline for total score and individual domain scores by treatment arm at each time point will be explored.

  • Number of participants reporting any serious adverse events [ Time Frame: Day 1 to 90 days post dose ] [ Designated as safety issue: Yes ]
  • Number of participants with anti-drug antibodies [ Time Frame: Week 5 ] [ Designated as safety issue: No ]
    The immunogenicity titer will be reported for samples confirmed positive for the presence of anti tremelimumab antibodies.

  • Tremelimumab blood concentration [ Time Frame: Week 5 ] [ Designated as safety issue: No ]
    Tremelimumab concentration data and summary statistics will be tabulated.

  • OS rate at 18 months [ Time Frame: Time from randomization until death, due to any cause, or alive at 18 months. ] [ Designated as safety issue: No ]

Estimated Enrollment: 677
Study Start Date: May 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tremelimumab
Tremelimumab
Drug: Tremelimumab
Tremelimumab is to be administered as an IV solution, followed by observation.
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo is to be administered as an IV solution, followed by observation.

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, and a 90-day follow-up period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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 treatment 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; - Measurable disease; - Adequate bone marrow, hepatic, and renal function

Exclusion Criteria:

  • 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;
  • 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;
  • 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 ≥ 2 from previous anticancer therapy; with the exception of vitiligo and alopecia.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01843374

Contacts
Contact: MedImmune Contact ClinicalTrialEnquiries@Medimmune.com

  Show 144 Study Locations
Sponsors and Collaborators
MedImmune LLC
  More Information

No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01843374     History of Changes
Other Study ID Numbers: D4880C00003
Study First Received: April 22, 2013
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
tremelimumab
pleural, peritoneal
malignant mesothelioma
CTLA-4

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 31, 2014