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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Sep 2013 → ongoing

Decision date (initial)

2024-07-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511841-20-00

EudraCT number

2012-003524-21

WHO UTN

U1111-1143-4798

ClinicalTrials.gov

NCT01843374

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Therapy, Safety

The primary objective is to compare the overall survival (OS) between the 2 treatment arms (tremelimumab and placebo) in subjects with unresectable malignant mesothelioma.

Secondary objectives 6

1. to estimate and compare OS rate at 18 months between the 2 treatment arms
2. to estimate and compare durable disease-control rate (DCR), progression-free survival (PFS), overall response rate (ORR) and duration of response between the 2 treatment arms
3. to evaluate the effect of tremelimumab on patient-reported outcomes (PROs).
4. to describe the safety and tolerability of tremelimumab in treated subjects.
5. to evaluate the immunogenicity of tremelimumab.
6. and to describe the pharmacokinetics (PK) of tremelimumab in treated subjects.

Conditions and MedDRA coding

unresectable pleural or peritoneal malignant mesothelioma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically and/or cytologically confirmed pleural or peritoneal malignant mesothelioma. Disease not amenable to curative surgery;
2. Age 18 and over at the time of consent;
3. ECOG Performance status 0-1;
4. 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 a platinum agent;
5. Recovered from all toxicities associated with prior treatment
6. Measurable disease
7. Adequate bone marrow, hepatic, and renal function
8. Negative screening test results for human immunodeficiency virus (HIV), hepatitis A, B and C.
9. 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;
10. 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;
11. 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.

Exclusion criteria 17

1. Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma
2. Received any prior monoclonal antibody 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;
4. Active, untreated central nervous system (CNS) metastasis;
5. 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;
6. Pregnant or breast feeding at time of consent;
7. Any condition that would prohibit the understanding or rendering of information and consent and compliance with the requirements of this protocol;
8. Active or history of diverticulitis. Note that diverticulosis is permitted;
9. 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;
10. History of sarcoidosis syndrome;
11. Currently receiving systemic corticosteroids or other immunosuppressive medications;
12. Subjects should not be vaccinated with live attenuated vaccines within one month prior to starting tremelimumab treatment;
13. The last dose of prior chemotherapy or radiation therapy (with the exception of palliative radiotherapy) was received less than 2 weeks prior to randomization;
14. Any unresolved toxicity from previous anticancer therapy;
15. 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;
16. 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);
17. Employees of the study site directly involved with the conduct of the study, or immediate family members of any such individuals.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is OS which is defined as the time from randomization until death due to any cause.

Secondary endpoints 3

1. The secondary efficacy endpoints include OS rate at 18 months, PRO as well as durable DCR, PFS, ORR, and duration of response, based on modified Response Evaluation Criteria in Solid Tumors (RECIST) for pleural mesothelioma and RECIST criteria v1.1 for peritoneal mesothelioma.
2. The safety endpoints include adverse events (AEs) and serious adverse events (SAEs), changes from baseline in clinical laboratory evaluations, electrocardiograms (ECGs), and vital signs. Adverse events and SAEs will be assessed for severity and relationship to investigational product.
3. The immunogenic potential of tremelimumab will be analyzed and the pharmacokinetics of tremelimumab will be assessed.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications