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 September 2014 by MedImmune LLC
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01843374
First received: April 22, 2013
Last updated: September 19, 2014
Last verified: September 2014

April 22, 2013
September 19, 2014
May 2013
April 2016   (final data collection date for primary outcome measure)
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.
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: Yes ]
The primary analysis of OS will be performed after a number of deaths have occurred among the approximately 180 participants randomized. For participants who are alive at the time of the primary analysis or lost to follow-up, OS will be censored on the last date when participants are known to be alive.
Complete list of historical versions of study NCT01843374 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 event [ 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.
Not Provided
Not Provided
 
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Unresectable Pleural or Peritoneal Malignant Mesothelioma
  • Drug: Tremelimumab
    Tremelimumab is to be administered as an IV solution, followed by observation.
  • Drug: Placebo
    Placebo is to be administered as an IV solution, followed by observation.
  • Experimental: Tremelimumab
    Tremelimumab
    Intervention: Drug: Tremelimumab
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
564
April 2016
April 2016   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: MedImmune Contact ClinicalTrialEnquiries@Medimmune.com
United States,   Australia,   Belgium,   Brazil,   Canada,   Denmark,   France,   Germany,   Hungary,   Israel,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Romania,   Russian Federation,   South Africa,   Spain,   Sweden,   United Kingdom
 
NCT01843374
D4880C00003
Yes
MedImmune LLC
MedImmune LLC
Not Provided
Not Provided
MedImmune LLC
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP