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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04334759
Ethics application status
Date submitted
1/04/2020
Date registered
2/04/2020
Date last updated
3/04/2020

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

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

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


Treatment: Drugs: Durvalumab
Durvalumab 1500 milligrams (mg) intravenous (IV) every 3 weeks + Cisplatin 75 mg/m² 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 IV every 3 weeks + Pemetrexed 500 mg/m² IV every 3 weeks) for 4 to 6 cycles, followed by Observation

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

Outcomes
Primary outcome [1] 0 0
Overall Survival - Defined as the time from randomisation to the date of death due to any cause.
Timepoint [1] 0 0
Minimum follow-up is 24 months after randomisation.
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) - Defined as the interval from date of randomisation to the date of first evidence of disease progression or death, whichever occurs first.
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) - Percentage of participants with either Complete Response (CR) or Partial Response (PR) assessed according to modified Response Criteria in Solid Tumors (RECIST) 1.1 for response in malignant pleural mesothelioma.
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 - Classify and grade participants abnormal laboratory values and/or adverse events.
Timepoint [3] 0 0
90 days after last dose of durvalumab or 30 days after last dose of chemotherapy, whichever is longer.
Secondary outcome [4] 0 0
Health-Related Quality of Life (QOL): QLQ-C30 - European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), Importance of QOL issues assessed using a four-point scale (1 = not at all, 4 = very much).
Timepoint [4] 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 [5] 0 0
Health-Related QOL: LC29 - 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).
Timepoint [5] 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 [6] 0 0
Health-Related QOL: EQ-5D-5L - 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).
Timepoint [6] 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 [7] 0 0
Health Care Usage Costs: Hospitalization - Australian Sites Only: Hospitalization costs calculated by applying Australian unit costs to Australian Refined Diagnostic Related Groups (AR DRG) costs for hospitalizations.
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 - Australian Sites Only: Scheduled costs for visits to health professionals collected via Medical Benefits Schedule (MBS).
Timepoint [8] 0 0
Minimum follow-up is 24 months after randomisation.
Secondary outcome [9] 0 0
Health Care Usage Costs: Medications - Australian Sites Only: Scheduled costs for medications collected via the Pharmaceutical Benefits Schedule (PBS).
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 malignant pleural
mesothelioma that is not amenable to curative surgical resection.

- Measurable disease as per modified RECIST 1.1 (mRECIST 1.1) criteria for assessment of
response in malignant 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 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) ≥ 60 mL/min (Cockcroft-Gault formula)

- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient 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
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior chemotherapy or other systemic anti-cancer or immunotherapy for MPM.

- Diagnosis on cytology or fine needle aspiration biopsy only.

- 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 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 (including durvalumab), 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, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.

- 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 durvalumab. Note: Local surgery of isolated lesions for palliative
intent is acceptable.

- 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 cisplatin administration.

- History of allergy or hypersensitivity to investigational product, cisplatin,
pemetrexed 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.

- 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
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

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
Australasian Lung Cancer Trials Group
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
Patients with malignant pleural mesothelioma (MPM) that cannot be surgically removed will
receive first-line treatment with standard chemotherapy of pemetrexed and cisplatin.
Two-thirds of the participants in the study will be randomly assigned to also receive a new
treatment called durvalumab.

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 MPM.
Trial website
https://clinicaltrials.gov/show/NCT04334759
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
Linda Miller- US Sites, BSN, RN
Address 0 0
Country 0 0
Phone 0 0
215-789-3621
Fax 0 0
Email 0 0
DREAM3R@precogllc.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04334759