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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01843374




Registration number
NCT01843374
Ethics application status
Date submitted
22/04/2013
Date registered
30/04/2013
Date last updated
10/05/2024

Titles & IDs
Public title
Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma
Scientific 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
Secondary ID [1] 0 0
2012-003524-21
Secondary ID [2] 0 0
D4880C00003
Universal Trial Number (UTN)
Trial acronym
Tremelimumab
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable Pleural or Peritoneal Malignant Mesothelioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Placebo

Experimental: Tremelimumab - Tremelimumab

Placebo Comparator: Placebo - Placebo


Treatment: Drugs: Tremelimumab
Tremelimumab is to be administered as an IV solution, followed by observation.

Treatment: Drugs: Placebo
Placebo is to be administered as an IV solution, followed by observation.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
3 years.
Secondary outcome [1] 0 0
OS Rate at 18 Months by Treatment Arm
Timepoint [1] 0 0
18 months
Secondary outcome [2] 0 0
Progression-free Survival by Treatment Arm
Timepoint [2] 0 0
Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.
Secondary outcome [3] 0 0
Overall Response Rate by Treatment Arm
Timepoint [3] 0 0
Time from randomization to best response to treatment, assessed up to 3 years.
Secondary outcome [4] 0 0
Duration of Response by Treatment Arm
Timepoint [4] 0 0
Duration of response from the first documentation of objcetive response (confirmed CR or PR) to the first documented disease progression, assessed up to 14 weeks after the initial response.
Secondary outcome [5] 0 0
Disease Control Rate by Treatment Arm
Timepoint [5] 0 0
Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.
Secondary outcome [6] 0 0
Durable Disease Control Rate by Treatment Arm
Timepoint [6] 0 0
Time from randomization to disease progression or death, whichever occurs first, assessed up to 3 years.
Secondary outcome [7] 0 0
Number of Participants Reporting Any Adverse Event
Timepoint [7] 0 0
Day 1- 90 days post dose
Secondary outcome [8] 0 0
Number of Participants Reporting Any Serious Adverse Events
Timepoint [8] 0 0
Day 1 to 90 days post dose
Secondary outcome [9] 0 0
Number of Participants With Positive Anti-drug Antibodies
Timepoint [9] 0 0
Week 5

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
Accrual to date
Final
571
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide
Recruitment hospital [2] 0 0
Research Site - Auchenflower
Recruitment hospital [3] 0 0
Research Site - Box Hill
Recruitment hospital [4] 0 0
Research Site - Chermside
Recruitment hospital [5] 0 0
Research Site - East Bentleigh
Recruitment hospital [6] 0 0
Research Site - Gosford
Recruitment hospital [7] 0 0
Research Site - Heidelberg
Recruitment hospital [8] 0 0
Research Site - Nedlands
Recruitment hospital [9] 0 0
Research Site - Saint Leonards
Recruitment hospital [10] 0 0
Research Site - Waratah
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
4032 - Chermside
Recruitment postcode(s) [5] 0 0
3165 - East Bentleigh
Recruitment postcode(s) [6] 0 0
2250 - Gosford
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment postcode(s) [9] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [10] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Belgium
State/province [15] 0 0
Edegem
Country [16] 0 0
Belgium
State/province [16] 0 0
Gent
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Denmark
State/province [20] 0 0
Copenhagen
Country [21] 0 0
France
State/province [21] 0 0
Caen Cedex
Country [22] 0 0
France
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Le Mans Cedex
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France
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Lille Cedex
Country [24] 0 0
France
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Nice
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France
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Rennes Cedex 9
Country [26] 0 0
France
State/province [26] 0 0
Toulouse
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France
State/province [27] 0 0
Villejuif Cedex
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Esslingen a.N.
Country [30] 0 0
Germany
State/province [30] 0 0
Freiburg
Country [31] 0 0
Germany
State/province [31] 0 0
Gauting
Country [32] 0 0
Germany
State/province [32] 0 0
Grosshansdorf
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Germany
State/province [34] 0 0
Hemer
Country [35] 0 0
Germany
State/province [35] 0 0
Karlsruhe
Country [36] 0 0
Germany
State/province [36] 0 0
Lubeck
Country [37] 0 0
Germany
State/province [37] 0 0
Löwenstein
Country [38] 0 0
Hungary
State/province [38] 0 0
Gyöngyös - Mátraháza
Country [39] 0 0
Hungary
State/province [39] 0 0
Törökbálint
Country [40] 0 0
Israel
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Beer Sheva
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Italy
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Alessandria
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Italy
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Aviano
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Italy
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Bergamo
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Italy
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Bologna
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Italy
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Candiolo
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Italy
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Genova
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Italy
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Meldola
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Italy
State/province [48] 0 0
Milano
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Italy
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Orbassano
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Italy
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Padova
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Italy
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Rozzano
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Italy
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Siena
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Korea, Republic of
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Jeonnam
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Korea, Republic of
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Seoul
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Netherlands
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Breda
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Netherlands
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Eindhoven
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Netherlands
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Rotterdam
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Poland
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Gdansk
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Poland
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Poznan
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Poland
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Szczecin
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Poland
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Warszawa
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Romania
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Craiova
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Russian Federation
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Moscow
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Russian Federation
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Nizhny Novgorod
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Russian Federation
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Saint-Petersburg
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South Africa
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Kraaifontein
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South Africa
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Pretoria
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Sabadell (Barcelona)
Country [71] 0 0
Spain
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San Sebastian
Country [72] 0 0
Spain
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Sevilla
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Sweden
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Linkoping
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Sweden
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Lund
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Sweden
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Umea
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United Kingdom
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Leeds
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United Kingdom
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Leicester
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United Kingdom
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London
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United Kingdom
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Maidstone
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United Kingdom
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Manchester
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United Kingdom
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Plymouth
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United Kingdom
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Southampton
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United Kingdom
State/province [83] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01843374
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01843374