NCT04334759 · REGISTRY CONDITION SEARCH

DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-10-01

Patients with pleural mesothelioma (PM) that cannot be surgically removed will receive standard chemotherapy (cisplatin or carboplatin and pemetrexed) given with durvalumab, a type of immunotherapy, or a treatment chosen by the study doctor, which is either standard chemotherapy or immunotherapy combination (ipilimumab and nivolumab). 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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Median Overall Survival (OS)

→

outcome · POSTED

Median Progression-Free Survival (PFS)

→

outcome · POSTED

Objective Tumour Response Rate (OTRR)

→

outcome · POSTED

Grade 3-5 Worst Degree Toxicity Rate

→

outcome · POSTED

Health-Related Quality of Life (QOL): LC29

→

outcome · POSTED

Health-Related QOL: EQ-5D-5L

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion Criteria: * Adults (18 years or over) with a histological diagnosis of epithelioid pleural mesothelioma that is not amenable to curative surgical resection. Histological diagnosis requires tumour tissue from an open biopsy, or a core biopsy with a needle of 19 gauge or wider. * 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: * Non-epithelioid histology (biphasic or sarcomatoid). * 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Durvalumab + Standard Chemotherapy for 4 to 6 cycles, followed by Maintenance with Durvalumab
intervention Names
Drug: Durvalumab
label
Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance
type
EXPERIMENTAL
description
Standard Chemotherapy for 4 to 6 cycles, followed by Observation
intervention Names
Drug: Standard Chemotherapy
label
Control Arm: Chemotherapy, then Observation
type
ACTIVE_COMPARATOR
description
Ipilimumab every 6 weeks and Nivolumab every 2 or 3 weeks for up to 2 years.
intervention Names
Drug: Ipilimumab and Nivolumab
label
Control Arm: Ipilimumab and Nivolumab
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance
description
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
name
Durvalumab
other Names
MEDI4736
Imfinzi
type
DRUG
arm Group Labels
Control Arm: Chemotherapy, then Observation
description
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
name
Standard Chemotherapy
other Names
Cisplatin or Carboplatin and Pemetrexed
type
DRUG
arm Group Labels
Control Arm: Ipilimumab and Nivolumab
description
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
name
Ipilimumab and Nivolumab
other Names
Yervoy, Opdivo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

intervention Model Description

First-line chemotherapy with cisplatin or carboplatin and pemetrexed + durvalumab OR physician's choice of either first-line chemotherapy alone, or ipilimumab and nivolumab.

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 214
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
OS based on the Kaplan-Meier method is defined as the duration from randomisation to the date of death due to any cause, or is censored at date last known alive.
measure
Median Overall Survival (OS)
time Frame
Minimum follow-up is 24 months after randomisation. Median follow-up for survival is of 33 months with range (3 months - 47 months).

secondary Outcomes

description
PFS based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) defined per modified RECIST 1.1 for PM and iRECIST, or death, or is censored at time of last disease assessment.
measure
Median Progression-Free Survival (PFS)
time Frame
Disease was evaluated at baseline, at weeks 6, 12, 18, 26, 34, 42, 50 and then every 12 weeks until disease progression (minimum follow-up is 24 months after randomisation). Median follow-up for survival is of 33 months with range (3 months - 47 months).
description
Objective tumour response rate (OTRR) is defined as the proportion of participants with a documented complete response, partial response (CR + PR) based on iRECIST criteria.
measure
Objective Tumour Response Rate (OTRR)
time Frame
Disease was evaluated at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50 and then every 12 weeks until disease progression (minimum follow-up is 24 months after randomisation). The treatment duration ranged from 0 to 36 months.
description
Adverse events (AEs) were graded per CTCAEv5 and the worst grade experienced per participant was recorded. The Grade 3-5 toxicity rate is defined as the proportion of treated participants whose worst grade AE was Grade 3, 4, or 5 at any point during the observation period, regardless of treatment attribution.
measure
Grade 3-5 Worst Degree Toxicity Rate
time Frame
AEs were recorded from randomisation until 30 days after last chemotherapy dose or 90 days after last durvalumab, ipilimumab, or nivolumab dose, whichever was longer. The treatment duration ranged from 0 to 36 months.
description
EORTC Quality of Life Lung Cancer Module (QLQ-LC29), Importance of QOL issues assessed using a four-point scale (1 = not at all, 4 = very much) and transformed to a 0-100 score, where higher scores mean worse possible symptom burden or severe impact.
measure
Health-Related Quality of Life (QOL): LC29
time Frame
Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50, then every 12 weeks until disease progression and at first progression visit (minimum follow-up is 24 months after randomisation).
description
Euro-Quality of Life (EuroQoL) 5 dimension 5 level (EQ-5D-5L) questionnaire, comprising of 5 questions with a score from 1 (no problem) to 5 (extreme problem) and a visual analog scale from 0 (worst) to 100 (best).
measure
Health-Related QOL: EQ-5D-5L
time Frame
Performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50, then every 12 weeks and at first progression visit until disease progression (minimum follow-up is 24 months after randomisation).

Full study description

brief Summary: Patients with pleural mesothelioma (PM) that cannot be surgically removed will receive standard chemotherapy (cisplatin or carboplatin and pemetrexed) given with durvalumab, a type of immunotherapy, or a treatment chosen by the study doctor, which is either standard chemotherapy or immunotherapy combination (ipilimumab and nivolumab). 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.
detailed Description: Mesothelioma is a malignant tumor of the mesothelial surfaces primarily arising in the thoracic pleura. In the United Kingdom and USA the expected number of cases in the next few decades are 65,000 and 85,000, respectively. Once diagnosed, this disease is rarely cured with a median survival of less than a year. 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.

Source references

references

citation
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.
pmid
35078853
type
BACKGROUND
citation
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.
pmid
34499875
type
DERIVED
citation
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.
pmid
33358660
type
DERIVED

Source notices and limitations

Discovery and provenance

release id
ctgov-registry-ed65b07fb707529eef6b84b3
edge id
nct-edge-040a0bd158689873c3b8
requested nct id
NCT04334759
primary nct id
NCT04334759
source kind
ctgov_condition_query
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Malignant+Mesothelioma&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true
source record id
Source null
source file sha256
a0f9e3b6357a244305bcd4f1497f354af250189cb3d89806f17b67c69f08f4e7
payload sha256
2ce69998a6559227d3a01226ebb74d160fe80d18359bfff0787654c2b3e83e25
payload
clinical indication matching status
condition_index_match_asserted_by_registry_not_reviewed
end exclusive
true
id
nct-edge-040a0bd158689873c3b8
link basis
returned_by_explicit_condition_and_posted_results_filter_query
nct id
NCT04334759
occurrences
context exact
NCT04334759
end
11
exact text
NCT04334759
start
0
offset unit
unicode_code_points
query cond
Malignant Mesothelioma
query disease state id
ds-malignant-mesothelioma
source file
/Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-10-20/clinicaltrials-condition/round-0000/raw/cond-malignant-mesothelioma-000.json
source file sha256
a0f9e3b6357a244305bcd4f1497f354af250189cb3d89806f17b67c69f08f4e7
source json pointer
/studies/37/protocolSection/identificationModule/nctId
source kind
ctgov_condition_query
source record id
Source null
source string basis
parsed_JSON_string_unmodified
source string sha256
aeef93ac45cccdb719b0645526f76144aec551f79a7487fd4986bc1ba341ac1b
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Malignant+Mesothelioma&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice