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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04334759




Registration number
NCT04334759
Ethics application status
Date submitted
2/04/2020
Date registered
6/04/2020

Titles & IDs
Public title
DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma
Scientific title
DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial
Secondary ID [1] 0 0
PrE0506
Secondary ID [2] 0 0
DREAM3R
Universal Trial Number (UTN)
Trial acronym
DREAM3R
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mesothelioma 0 0
Pleural Mesothelioma 0 0
Malignant Pleural Mesothelioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab
Treatment: Drugs - Standard Chemotherapy
Treatment: Drugs - Ipilimumab and Nivolumab

Experimental: Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance - Durvalumab + Standard Chemotherapy for 4 to 6 cycles, followed by Maintenance with Durvalumab

Active comparator: Control Arm: Chemotherapy, then Observation - Standard Chemotherapy for 4 to 6 cycles, followed by Observation

Active comparator: Control Arm: Ipilimumab and Nivolumab - Ipilimumab every 6 weeks and Nivolumab every 2 or 3 weeks for up to 2 years.


Treatment: Drugs: 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

Treatment: Drugs: 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

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Effects on Overall Survival
Timepoint [1] 0 0
Minimum follow-up is 24 months after randomisation.
Secondary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
Performed 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).
Secondary outcome [2] 0 0
Objective Tumour Response Rate (OTRR)
Timepoint [2] 0 0
Performed 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).
Secondary outcome [3] 0 0
Classify and grade participants adverse events as assessed by CTCAE V5.0
Timepoint [3] 0 0
90 days after last dose of immunotherapy or 30 days after last dose of chemotherapy, whichever is longer.
Secondary outcome [4] 0 0
Health-Related Quality of Life (QOL): QLQ-C30
Timepoint [4] 0 0
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).
Secondary outcome [5] 0 0
Health-Related QOL: LC29
Timepoint [5] 0 0
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).
Secondary outcome [6] 0 0
Health-Related QOL: EQ-5D-5L
Timepoint [6] 0 0
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).
Secondary outcome [7] 0 0
Health Care Usage Costs: Hospitalization
Timepoint [7] 0 0
Minimum follow-up is 24 months after randomisation.
Secondary outcome [8] 0 0
Health Care Usage Costs: Scheduled Visits to Health Professionals
Timepoint [8] 0 0
Minimum follow-up is 24 months after randomisation.
Secondary outcome [9] 0 0
Health Care Usage Costs: Medications
Timepoint [9] 0 0
Minimum follow-up is 24 months after randomisation.

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

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
18/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
Accrual to date
Final
214
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [4] 0 0
Coffs Harbour Health Campus - Coffs Harbour
Recruitment hospital [5] 0 0
Gosford Hospital - Gosford
Recruitment hospital [6] 0 0
Wyong Hospital - Hamlyn Terrace
Recruitment hospital [7] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [8] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [9] 0 0
Orange Health Service - Orange
Recruitment hospital [10] 0 0
Northern Cancer Institute (GenesisCare) - Saint Leonards
Recruitment hospital [11] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [12] 0 0
Westmead Hospital - Westmead
Recruitment hospital [13] 0 0
Icon Cancer Care Wesley - Auchenflower
Recruitment hospital [14] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [15] 0 0
Icon Cancer Care Chermside - Chermside
Recruitment hospital [16] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [17] 0 0
Townsville University Hospital - Douglas
Recruitment hospital [18] 0 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [19] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [20] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [21] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [22] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [23] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [24] 0 0
Monash Health - Clayton
Recruitment hospital [25] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [26] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [27] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [28] 0 0
Epworth HealthCare - Richmond - Richmond
Recruitment hospital [29] 0 0
Sunshine Hospital (Western Health) - Saint Albans
Recruitment hospital [30] 0 0
Goulburn Valley Health - Shepparton
Recruitment hospital [31] 0 0
Sir Charles Gairdner Hospital (SCGH) - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2148 - Blacktown
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [5] 0 0
2250 - Gosford
Recruitment postcode(s) [6] 0 0
2259 - Hamlyn Terrace
Recruitment postcode(s) [7] 0 0
2747 - Kingswood
Recruitment postcode(s) [8] 0 0
2170 - Liverpool
Recruitment postcode(s) [9] 0 0
2800 - Orange
Recruitment postcode(s) [10] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [11] 0 0
2298 - Waratah
Recruitment postcode(s) [12] 0 0
2145 - Westmead
Recruitment postcode(s) [13] 0 0
4066 - Auchenflower
Recruitment postcode(s) [14] 0 0
4575 - Birtinya
Recruitment postcode(s) [15] 0 0
4032 - Chermside
Recruitment postcode(s) [16] 0 0
4814 - Douglas
Recruitment postcode(s) [17] 0 0
4101 - South Brisbane
Recruitment postcode(s) [18] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [19] 0 0
5042 - Bedford Park
Recruitment postcode(s) [20] 0 0
5011 - Woodville South
Recruitment postcode(s) [21] 0 0
7000 - Hobart
Recruitment postcode(s) [22] 0 0
7250 - Launceston
Recruitment postcode(s) [23] 0 0
3168 - Clayton
Recruitment postcode(s) [24] 0 0
3199 - Frankston
Recruitment postcode(s) [25] 0 0
3084 - Heidelberg
Recruitment postcode(s) [26] 0 0
3000 - Melbourne
Recruitment postcode(s) [27] 0 0
3121 - Richmond
Recruitment postcode(s) [28] 0 0
3021 - Saint Albans
Recruitment postcode(s) [29] 0 0
3630 - Shepparton
Recruitment postcode(s) [30] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
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
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
New Zealand
State/province [15] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
PrECOG, LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Thoracic Oncology Group Australasia (TOGA)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
University of Sydney
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Patrick Forde, MD
Address 0 0
Johns Hopkins University
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data is proprietary


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04334759