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DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma (DREAM3R)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04334759
Recruitment Status : Not yet recruiting
First Posted : April 6, 2020
Last Update Posted : December 1, 2020
Sponsor:
Collaborators:
AstraZeneca
Australasian Lung Cancer Trials Group
University of Sydney
Information provided by (Responsible Party):
PrECOG, LLC.

Tracking Information
First Submitted Date  ICMJE April 2, 2020
First Posted Date  ICMJE April 6, 2020
Last Update Posted Date December 1, 2020
Estimated Study Start Date  ICMJE February 2021
Estimated Primary Completion Date April 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2020)
Overall Survival [ Time Frame: Minimum follow-up is 24 months after randomisation. ]
Defined as the time from randomisation to the date of death due to any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2020)
  • Progression-Free Survival (PFS) [ Time Frame: 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). ]
    Defined as the interval from date of randomisation to the date of first evidence of disease progression or death, whichever occurs first.
  • Objective Tumour Response Rate (OTRR) [ Time Frame: 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). ]
    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.
  • Classify and grade participants adverse events as assessed by CTCAE V5.0 [ Time Frame: 90 days after last dose of durvalumab or 30 days after last dose of chemotherapy, whichever is longer. ]
    Classify and grade participants abnormal laboratory values and/or adverse events.
  • Health-Related Quality of Life (QOL): QLQ-C30 [ Time Frame: 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). ]
    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).
  • Health-Related QOL: LC29 [ Time Frame: 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). ]
    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).
  • Health-Related QOL: EQ-5D-5L [ Time Frame: 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). ]
    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).
  • Health Care Usage Costs: Hospitalization [ Time Frame: Minimum follow-up is 24 months after randomisation. ]
    Australian Sites Only: Hospitalization costs calculated by applying Australian unit costs to Australian Refined Diagnostic Related Groups (AR DRG) costs for hospitalizations.
  • Health Care Usage Costs: Scheduled Visits to Health Professionals [ Time Frame: Minimum follow-up is 24 months after randomisation. ]
    Australian Sites Only: Scheduled costs for visits to health professionals collected via Medical Benefits Schedule (MBS).
  • Health Care Usage Costs: Medications [ Time Frame: Minimum follow-up is 24 months after randomisation. ]
    Australian Sites Only: Scheduled costs for medications collected via the Pharmaceutical Benefits Schedule (PBS).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DuRvalumab With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma
Official Title  ICMJE DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial
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.

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 2:1 to receive durvalumab with standard chemotherapy or to receive standard chemotherapy alone.

Arm A: Durvalumab every 3 weeks + standard chemotherapy (Cisplatin every 3 weeks + Pemetrexed every 3 weeks) for 4 to 6 cycles, followed by Durvalumab every 4 weeks.

Arm B: Standard chemotherapy (Cisplatin every 3 weeks + Pemetrexed every 3 weeks) for 4 to 6 cycles followed by observation.

Treatment with durvalumab in Arm A will continued until disease progression, unacceptable toxicity or patient withdrawal.

Tumor assessments and Quality of Life forms will be performed at baseline, then at weeks 6, 12, 18, 26, 34, 42, 50 and then every 12 weeks until disease 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 baseline, day 1 of cycle 2, and day 1 of cycle 3 will be done.

The study is being led jointly by PrECOG as the US sponsor and University of Sydney as the international sponsor

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
First-line chemotherapy with cisplatin and pemetrexed +/- durvalumab.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Mesothelioma
  • Pleural Mesothelioma
  • Malignant Pleural Mesothelioma
Intervention  ICMJE
  • Drug: 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
    Other Names:
    • MEDI4736
    • Imfinzi
  • Drug: 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
    Other Name: Cisplatin and Pemetrexed
Study Arms  ICMJE
  • Experimental: Arm A: Durvalumab + Chemotherapy, then Durvalumab Maintenance
    Durvalumab + Standard Chemotherapy for 4 to 6 cycles, followed by Maintenance with Durvalumab
    Intervention: Drug: Durvalumab
  • Active Comparator: Arm B: Chemotherapy, then Observation
    Standard Chemotherapy for 4 to 6 cycles, followed by Observation
    Intervention: Drug: Standard Chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 2, 2020)
480
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date April 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Linda Miller- US Sites, BSN, RN 215-789-3621 DREAM3R@precogllc.org
Contact: Ailsa Langford- International Sites 61-2-9562-5000 dream3r@ctc.usyd.au
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04334759
Other Study ID Numbers  ICMJE DREAM3R
PrE0506 ( Other Identifier: PrECOG, LLC )
ALTG 18/001 ( Other Identifier: Australasian Lung Cancer Trials Group )
CTC 0231 ( Other Identifier: NHMRC Clinical Trials Centre, University of Sydney )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Data is proprietary
Responsible Party PrECOG, LLC.
Study Sponsor  ICMJE PrECOG, LLC.
Collaborators  ICMJE
  • AstraZeneca
  • Australasian Lung Cancer Trials Group
  • University of Sydney
Investigators  ICMJE
Study Chair: Patrick Forde, MD Johns Hopkins University
Study Chair: Anna Nowak, MD Faculty of Health and Medical Sciences University of Western Australia
PRS Account PrECOG, LLC.
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP