DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma
NCT ID: NCT04334759
Last Updated: 2026-01-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
214 participants
INTERVENTIONAL
2021-02-18
2025-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Durvalumab is an antibody (a type of human protein) that works by blocking a body substance called Programmed Death-Ligand 1 (PD-L1). Blocking PD-L1 helps the body's immune system attack cancer cells. Research has shown that durvalumab can slow tumor growth and shrink tumors in some people with cancer. Previous studies of combining durvalumab and chemotherapy showed that this combination is active in advanced mesothelioma.
The purpose of this study is to see whether adding durvalumab to standard chemotherapy will improve overall survival (OS) in patients with PM.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Clinical Trial of Durvalumab (MEDI4736) as 1st Line Therapy in Advanced Non-small Cell Lung Cancer Patients
NCT02879617
Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC
NCT03057106
A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
NCT03963414
Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy
NCT03703297
ADMIRAL Trial: Adaptive Mediastinal Radiation With Chemo-Immunotherapy
NCT04372927
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
This is an International, Open-Label, Multi-center, Phase III study. Patients will be randomized 1:1 to receive (a) chemotherapy given with durvalumab versus (b) physician's choice of either chemotherapy alone, or ipilimumab and nivolumab.
Experimental Arm:
\- Durvalumab every 3 weeks + standard chemotherapy (cisplatin or carboplatin every 3 weeks + pemetrexed every 3 weeks) for 4 to 6 cycles, followed by durvalumab every 4 weeks until disease progression, unacceptable toxicity or patient withdrawal.
Control Arm: Physician Choice
* Standard chemotherapy (cisplatin or carboplatin every 3 weeks + pemetrexed every 3 weeks) for 4 to 6 cycles followed by observation
* Ipilimumab every 6 weeks and nivolumab every 2 or 3 weeks \[physician discretion\] for up to 2 years until disease progression, unacceptable toxicity or patient withdrawal .
Tumor assessments and Quality of Life (QOL) forms will be performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50 and then every 12 weeks until disease progression. The QOL forms will also be repeated during the first visit after progression.
Mandatory pre-treatment tumor tissue sample (i.e., obtained during a previous procedure or biopsy) for research will also be required. Blood samples for research at 3 time points will be done.
The study is being led jointly by PrECOG as the US sponsor and University of Sydney as the international sponsor.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance
Durvalumab + Standard Chemotherapy for 4 to 6 cycles, followed by Maintenance with Durvalumab
Durvalumab
Durvalumab 1500 milligrams (mg) intravenous (IV) every 3 weeks + Cisplatin 75 mg/m² or Carboplatin AUC 5 IV every 3 weeks + Pemetrexed 500 mg/m² IV every 3 weeks for 4 to 6 cycles, followed by maintenance with Durvalumab 1500 mg IV every 4 weeks
Control Arm: Chemotherapy, then Observation
Standard Chemotherapy for 4 to 6 cycles, followed by Observation
Standard Chemotherapy
Cisplatin 75 mg/m² or Carboplatin AUC 5 IV every 3 weeks + Pemetrexed 500 mg/m² IV every 3 weeks) for 4 to 6 cycles, followed by Observation
Control Arm: Ipilimumab and Nivolumab
Ipilimumab every 6 weeks and Nivolumab every 2 or 3 weeks for up to 2 years.
Ipilimumab and Nivolumab
Ipilimumab 1 mg/kg every 6 weeks and Nivolumab 360 mg every 3 weeks or 3 mg/kg every 2 weeks for up to 2 years
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Durvalumab
Durvalumab 1500 milligrams (mg) intravenous (IV) every 3 weeks + Cisplatin 75 mg/m² or Carboplatin AUC 5 IV every 3 weeks + Pemetrexed 500 mg/m² IV every 3 weeks for 4 to 6 cycles, followed by maintenance with Durvalumab 1500 mg IV every 4 weeks
Standard Chemotherapy
Cisplatin 75 mg/m² or Carboplatin AUC 5 IV every 3 weeks + Pemetrexed 500 mg/m² IV every 3 weeks) for 4 to 6 cycles, followed by Observation
Ipilimumab and Nivolumab
Ipilimumab 1 mg/kg every 6 weeks and Nivolumab 360 mg every 3 weeks or 3 mg/kg every 2 weeks for up to 2 years
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Measurable disease as per modified RECIST 1.1 (mRECIST 1.1) criteria for assessment of response in pleural mesothelioma, without prior radiotherapy to these sites.
* Body weight \>30 kg,
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Tumour tissue (Formalin-Fixed Paraffin-Embedded \[FFPE\]) available from standard of care diagnostic biopsy for PD-L1 testing and other correlative biomarker testing at a central laboratory.
* Life expectancy of at least 12 weeks.
* Adequate blood tests (done within 14 days prior to randomisation) and with values within the ranges specified below. Blood transfusions are permissible if completed at least 7 days prior to treatment start.
* Haemoglobin ≥ 9.0 g/L
* Absolute neutrophil count ≥ 1.5 x 10\^9/L
* Platelets ≥ 100 x 10\^9/L
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except participants with Gilbert's Syndrome, who are eligible with bilirubin ≤ 2.5 ULN)
* Alanine transaminase ≤ 2.5 x upper limit of normal (ULN), unless liver metastases or invasion are present, in which case it must be ≤ 5 x ULN
* Aspartate aminotransferase ≤ 2.5 x ULN, unless liver metastases or invasion are present, in which case it must be ≤ 5 x ULN
* Creatinine clearance (CrCl) ≥ 45 mL/min (Cockcroft-Gault formula). NOTE: Carboplatin AUC 5 must be the initial platinum agent of choice in patients with creatinine Cl \<60 mL/min but ≥ 45 mL/min, or those with clinically reported hearing loss.
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient or legal representative must sign a consent form prior to enrolment in the trial to document their willingness to participate.
* Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
* Women of childbearing potential must use a reliable means of contraception during treatment and for at least 90 days thereafter. Breastfeeding is not permissible during or for at least 90 days after the final study treatment. Men must have been surgically sterilised or use a barrier method of contraception if they are sexually active with a woman of child bearing potential.
* Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
Exclusion Criteria
* Prior chemotherapy or other systemic anti-cancer or immunotherapy for PM.
* Diagnosis based only on cytology or aspiration biopsy with a needle narrower than 19 gauge.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g. colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included
5. Patients with celiac disease controlled by diet alone
* Any condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 28 days of durvalumab or ipilimumab or nivolumab administration. Intranasal, inhaled or topical steroids or local steroid injections (e.g. intra-articular injection) are permitted in the absence of active autoimmune disease. Standard steroid premedication given prior to chemotherapy or as prophylaxis for imaging contrast allergy should not be counted for this criterion.
* Participants with symptomatic or uncontrolled brain metastases or leptomeningeal disease are excluded.
* Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
* Current treatment or treatment within the last 12 months with any investigational anti-cancer products.
* Concurrent enrolment in another clinical study testing an anticancer treatment.
* Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
* Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment on protocol. Note: Local surgery of isolated lesions for palliative intent is acceptable. Limited pleural biopsy procedures do not apply.
* No other malignancy that requires active treatment. Participants with a past history of adequately treated carcinoma in situ, non-melanoma skin cancer or lentigo maligna without evidence of disease or superficial transitional cell carcinoma of the bladder are eligible.
* Hearing loss or peripheral neuropathy considered by the investigators to contraindicate administration of either cisplatin, carboplatin or pemetrexed.
* History of allergy or hypersensitivity to investigational product, cisplatin, carboplatin, pemetrexed, ipilimumab, nivolumab or any excipient.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive cardiac failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, active peptic ulcer disease or gastritis, serious chronic gastrointestinal conditions associated with diarrhoea, active bleeding diatheses.
* Hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Exceptions include past or resolved Hepatitis B (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) and patients positive for hepatitis C (HCV) antibody if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in absence of clinical suspicion of HIV.
* Known history of primary immunodeficiency, allogeneic organ transplant, pneumonitis or active tuberculosis.
* Receipt of live attenuated vaccination within 30 days prior to enrolment or within 30 days of receiving durvalumab, ipilimumab, nivolumab.
* Specific comorbidities or conditions or concomitant medications which may interact with the investigational product(s).
* Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
* Serious medical or psychiatric conditions or social situation that might limit compliance with study requirements, substantially increase risk of incurring adverse events or compromise the ability of the patient to give written informed consent.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
AstraZeneca
INDUSTRY
Thoracic Oncology Group Australasia (TOGA)
UNKNOWN
University of Sydney
OTHER
PrECOG, LLC.
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Patrick Forde, MD
Role: STUDY_CHAIR
Johns Hopkins University
Anna Nowak, MD
Role: STUDY_CHAIR
Faculty of Health and Medical Sciences University of Western Australia
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California San Diego
La Jolla, California, United States
University of Miami
Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University
Atlanta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
NorthShore University Health System/Kellogg Cancer Center
Evanston, Illinois, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Massaschusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Morristown Medical/Atlantic Health
Morristown, New Jersey, United States
Jersey Shore University Medical Center
Neptune City, New Jersey, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Memorial Sloan Kettering
New York, New York, United States
University of Cincinnati
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
The Ohio State University
Columbus, Ohio, United States
Penn State Cancer Institute
Hershey, Pennsylvania, United States
Abramson Cancer Cener at Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States
Allegheny Cancer Center
Pittsburgh, Pennsylvania, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
University of Virginia
Charlottesville, Virginia, United States
Canberra Hospital
Garran, Australian Capital Territory, Australia
Blacktown Hospital
Blacktown, New South Wales, Australia
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia
Coffs Harbour Health Campus
Coffs Harbour, New South Wales, Australia
Gosford Hospital
Gosford, New South Wales, Australia
Wyong Hospital
Hamlyn Terrace, New South Wales, Australia
Nepean Hospital
Kingswood, New South Wales, Australia
Liverpool Hospital
Liverpool, New South Wales, Australia
Orange Health Service
Orange, New South Wales, Australia
Northern Cancer Institute (GenesisCare)
Saint Leonards, New South Wales, Australia
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Icon Cancer Care Wesley
Auchenflower, Queensland, Australia
Sunshine Coast University Hospital
Birtinya, Queensland, Australia
Icon Cancer Care Chermside
Chermside, Queensland, Australia
The Prince Charles Hospital
Chermside, Queensland, Australia
Townsville University Hospital
Douglas, Queensland, Australia
Icon Cancer Care South Brisbane
South Brisbane, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Launceston General Hospital
Launceston, Tasmania, Australia
Monash Health
Clayton, Victoria, Australia
Peninsula & South Eastern Haematology and Oncology Group
Frankston, Victoria, Australia
Austin Hospital
Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Epworth HealthCare - Richmond
Richmond, Victoria, Australia
Sunshine Hospital (Western Health)
Saint Albans, Victoria, Australia
Goulburn Valley Health
Shepparton, Victoria, Australia
Sir Charles Gairdner Hospital (SCGH)
Nedlands, Western Australia, Australia
Auckland City Hospital
Grafton, Auckland, New Zealand
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Kok PS, Forde PM, Hughes B, Sun Z, Brown C, Ramalingam S, Cook A, Lesterhuis WJ, Yip S, O'Byrne K, Pavlakis N, Brahmer J, Anagnostou V, Ford K, Fitzpatrick K, Bricker A, Cummins MM, Stockler M, Nowak AK; Thoracic Oncology Group of Australasia (TOGA) and PrECOG, USA. Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial. BMJ Open. 2022 Jan 25;12(1):e057663. doi: 10.1136/bmjopen-2021-057663.
Kindler HL. Understanding the new therapeutic options for mesothelioma. Lancet Oncol. 2021 Oct;22(10):1353-1355. doi: 10.1016/S1470-2045(21)00520-9. Epub 2021 Sep 6. No abstract available.
Uprety D. CheckMate 743: A Glimmer of Hope for Malignant Pleural Mesothelioma. Clin Lung Cancer. 2021 Mar;22(2):71-73. doi: 10.1016/j.cllc.2020.11.009. Epub 2020 Dec 2. No abstract available.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
PrE0506
Identifier Type: OTHER
Identifier Source: secondary_id
TOGA 18/001
Identifier Type: OTHER
Identifier Source: secondary_id
CTC 0231
Identifier Type: OTHER
Identifier Source: secondary_id
DREAM3R
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.