Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001170415
Ethics application status
Approved
Date submitted
22/08/2016
Date registered
26/08/2016
Date last updated
23/02/2024
Date data sharing statement initially provided
12/11/2018
Date results provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 2 trial of durvalumab with first line chemotherapy in mesothelioma with a safety run in.
Scientific title
A phase 2 trial of durvalumab with first line chemotherapy in mesothelioma with a safety run in.

Secondary ID [1] 289567 0
CTC 0142/ALTG 15/003
Universal Trial Number (UTN)
Trial acronym
DREAM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Mesothelioma (MPM). 299297 0
Condition category
Condition code
Cancer 299292 299292 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A safety run-in phase will be conducted to confirm the tolerability of the standard dose of durvalumab. The safety run-in of the study will be done at a limited number of study sites, once the durvalumab dose is confirmed recruitment will be expanded to all sites for the remainder of the trial.

Durvalumab 1125mg (dose to be confirmed by safety run in) AND chemotherapy (cisplatin 75mg/m2 and pemetrexed 500 mg/m2) are all given intravenously (IV) on day 1, repeated every 3 weeks for a maximum of 6 cycles. If there is no progression, continue durvalumab 1125mg IV on day 1 every 3 weeks for a maximum of an additional 12 cycles (18 cycles in total).

The study intervention will be delivered by experienced medical oncologists and their teams within a hospital based treatment facility.
Intervention code [1] 295164 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298784 0
Progression free survival at 6 months (PFS6) according to mRECIST for MPM.
Timepoint [1] 298784 0
6 months PFS measured from the date of trial entry until the date that disease progression is first observed, or the date of death from any cause, whichever occurs first.
Secondary outcome [1] 325190 0
The objective tumour response rate is defined as the proportion (percentage) of participants with a confirmed response of either Complete Response (CR) or Partial Response (PR) assessed by the investigator according to modified RECIST criteria for assessment of response in malignant pleural mesothelioma and according to modified immune-related response criteria (modified irRC).
Timepoint [1] 325190 0
For each participant, objective response will be based on evaluable response assessments performed up until progression or commencement of non-protocol anti-cancer therapy, whichever occurs first.
Secondary outcome [2] 326610 0
Frequency and severity of adverse events (as per CTCAE v4.03).
Timepoint [2] 326610 0
Adverse Events will be recorded from the first dose of study treatment until 90 days after cessation of study treatment.
Secondary outcome [3] 326611 0
Progression free survival (PFS) according to mRECIST for MPM and mirRC.
Timepoint [3] 326611 0
PFS is measured from the date of registration until the date that disease progression is first observed, or the date of death from any cause, whichever occurs first. The date of first disease progression based on imaging is that of the first positive scan, even if this is determined in retrospect.
Secondary outcome [4] 326612 0
Overall survival (OS).
Timepoint [4] 326612 0
OS is defined as the interval from the date of registration to the date of death from any cause.
Secondary outcome [5] 366477 0
Tertiary exploratory outcome: Associations between clinical outcomes and potential predictive/prognostic biomarkers (including but not limited to STAT activation, leucocyte sub-sets, tumour PD-L1 expression, T cell receptor repertoire and tumour gene expression signatures).
Timepoint [5] 366477 0
At EOS (2 years post enrolment of final patient)

Eligibility
Key inclusion criteria
1. Adults (18 years or over) with a histological or cytological diagnosis of malignant pleural mesothelioma that is not amendable to curative surgical resection
2. Measurable disease as per modified RECIST criteria for assessment of response in malignant pleural mesothelioma
3. ECOG performance status of 0 or 1
4. Tumour tissue (FFPE) available for PD-L1 testing at a central laboratory
5. Must have measurable disease without prior radiotherapy to these sites
6. Adequate bone marrow function (done within 28 days prior to registration and with values within the ranges specified below). Blood transfusions are permissible.
* Haemoglobin greater than or equal to 90 g/L
* Absolute neutrophil count greater than or equal to 1.5 x 109/L
* Platelets greater than or equal to 100 x 109/L
7. Adequate liver function (done within 28 days prior to registration and with values within the ranges specified below):
* Alanine transaminase less than or equal to 3 x upper limit of normal (ULN), unless liver metastases or invasion are present, in which case it must be less than or equal to 5 x ULN
* Aspartate aminotransferase less than or equal to 3 x ULN, unless liver metastases or invasion are present, in which case it must be less than or equal to 5 x ULN
* Total bilirubin less than or equal to 1.5 x ULN (except participants with Gilbert’s Syndrome, who are eligible with bilirubin less than or equal to 2.5 ULN)
8. Adequate renal function (done within 28 days prior to registration and with values within the ranges specified below):
* Serum creatinine less than or equal to 1.5 x ULN
or
* Creatinine clearance (CrCl) greater than or equal to 60 mL/min (use Cockroft-Gault formula)
9. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
10. Signed, written informed consent
11. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative serum pregnancy test done within 24 hours prior to enrolment. Men must have been surgically sterilised or use a (double if required) barrier method of contraception if they are sexually active with a woman of child bearing potential.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior chemotherapy or other systemic anti-cancer or immunotherapy for MPM
2. Active, known or suspected autoimmune disease. Participants are not excluded if they have vitiligo, type 1 diabetes mellitus, Grave’s disease, residual hypothyroidism due to an autoimmune condition requiring only hormone replacement, or psoriasis not requiring systemic treatment within the past 2 years.
3. Any condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 28 days of durvalumab administration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease.
4. Participants with symptomatic or uncontrolled brain metastases or leptomeningeal disease are excluded. Controlled brain metastases are those which have been treated and are radiologically and/or clinically stable, and the patient is asymptomatic and does not require corticosteroids.
5. 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
6. Current treatment or treatment within the last 12 months with any investigational products
7. Life expectancy of less than 24 weeks
8. History of another malignancy within 5 years prior to enrolment. Participants with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Participants with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment.
9. Mean QT interval corrected for heart rate (QTc) greater than or equal to 470 ms calculated from 3 electrocardiograms using Fridericia’s Correction (QTc equal to QT/RR1/3)
10. Hearing loss or peripheral neuropathy considered by the investigators to contraindicate cisplatin administration
11. History of hypersensitivity to investigational product, cisplatin/pemetrexed or any excipient
12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive cardiac failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, hepatitis B, hepatitis C or human immunodeficiency virus
13. Known history of interstitial lung disease from any cause
14. Known history of primary immunodeficiency, allogeneic organ transplant, inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis), pneumonitis or active tuberculosis
15. Receipt of live attenuated vaccination within 30 days prior to enrolment or within 30 days of receiving durvalumab
16. Specific comorbidities or conditions or concomitant medications which may interact with the investigational product(s)
17. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
18. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The study will begin with an initial safety run-in using a 3+3 design and an expected accrual of 6 participants. These participants will be included in the total sample size of 54 evaluable participants, consisting of 31 recruited in stage 1, and another 23 recruited in stage 2. The null hypothesis is that the true PFS6 rate is 45%, which is in keeping with standard therapy and would be considered not worthy of further evaluation. With a one-sided type I error rate of 5%, the two-stage design provides greater than 90% power if the true PFS6 rate is 65% (alternate hypothesis).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2016
Actual
28/12/2016
Date of last participant enrolment
Anticipated
31/10/2018
Actual
27/09/2017
Date of last data collection
Anticipated
31/10/2019
Actual
27/09/2019
Sample size
Target
54
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 6450 0
Northern Cancer Institute - St Leonards
Recruitment hospital [2] 6451 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [3] 6452 0
Coffs Harbour Base Hospital - Coffs Harbour
Recruitment hospital [4] 6453 0
Nepean Hospital - Kingswood
Recruitment hospital [5] 6455 0
The Prince Charles Hospital - Chermside
Recruitment hospital [6] 6456 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 6457 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 6459 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [9] 6462 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 14004 0
2050 - Camperdown
Recruitment postcode(s) [2] 14005 0
2450 - Coffs Harbour
Recruitment postcode(s) [3] 14008 0
4032 - Chermside
Recruitment postcode(s) [4] 14009 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 14010 0
5042 - Bedford Park
Recruitment postcode(s) [6] 14012 0
3084 - Heidelberg
Recruitment postcode(s) [7] 14015 0
6009 - Nedlands
Recruitment postcode(s) [8] 14095 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 294273 0
Commercial sector/Industry
Name [1] 294273 0
AstraZeneca Pty Ltd
Country [1] 294273 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
NHMRC Clinical Trials Centre
Level 6, Medical Foundation Bld (K25)
92-94 Parramatta Rd
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 293109 0
None
Name [1] 293109 0
N/A
Address [1] 293109 0
N/A
Country [1] 293109 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295705 0
SLHD Ethics Committee (RPAH zone)
Ethics committee address [1] 295705 0
Ethics committee country [1] 295705 0
Australia
Date submitted for ethics approval [1] 295705 0
06/06/2016
Approval date [1] 295705 0
09/08/2016
Ethics approval number [1] 295705 0
X-16-0234 and HREC/16/RPAH/287

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

Contacts
Principal investigator
Name 67014 0
Prof Anna Nowak
Address 67014 0
Sir Charles Gairdner Hospital
c/o Medical Oncology
Hospital Ave
Nedlands
WA 6009
Country 67014 0
Australia
Phone 67014 0
+61 8 6151 1078
Fax 67014 0
Email 67014 0
[email protected]
Contact person for public queries
Name 67015 0
DREAM Trial Operations Coordinator
Address 67015 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown
NSW 1450
Country 67015 0
Australia
Phone 67015 0
+61 2 9562 5000
Fax 67015 0
Email 67015 0
[email protected]
Contact person for scientific queries
Name 67016 0
Anna Nowak
Address 67016 0
Sir Charles Gairdner Hospital
c/o Medical Oncology
Hospital Ave
Nedlands
WA 6009
Country 67016 0
Australia
Phone 67016 0
+61 8 6151 1078
Fax 67016 0
Email 67016 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Participant data supporting the publication results. Consent to provide case level data has not been obtained. IPD may be shared where a specific secondary research proposal receives a waiver of consent from our ethics committee.
When will data be available (start and end dates)?
Data are available for an indefinite time
Start date: January 2024
End date: Unknown
Available to whom?
Data are potentially available to any research organisation or researcher with a valid ethics approval to conduct desired research based in Australia and New Zealand.
Available for what types of analyses?
Any type of analysis
How or where can data be obtained?
As of 1st July 2023, access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health). Search for the ACTRN number in the catalogue to find datasets associated with this trial.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
21735Data dictionary  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseImmunotherapy in MPM.2017
EmbaseBiomarkers in malignant pleural mesothelioma: Current status and future directions.2018https://dx.doi.org/10.21037/jtd.2018.04.31
Dimensions AIOA07.07 PFS and OS Beyond 5 years of NSCLC Patients with Synchronous Oligometastases Treated in a Prospective Phase II Trial (NCT 01282450)2018https://doi.org/10.1016/j.jtho.2018.08.274
Dimensions AIOA08.01 Long-Term Efficacy and Safety of Nivolumab in Second- or Third-Line Japanese Malignant Pleural Mesothelioma Patients (Phase II: MERIT Study)2018https://doi.org/10.1016/j.jtho.2018.08.275
Dimensions AIOA08.02 DREAM - A Phase 2 Trial of Durvalumab with First Line Chemotherapy in Mesothelioma: Final Result2018https://doi.org/10.1016/j.jtho.2018.08.276
EmbaseA multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial.2020https://dx.doi.org/10.1016/j.annonc.2020.09.009
EmbaseDurvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in.2020https://dx.doi.org/10.1016/S1470-2045%2820%2930462-9
EmbaseFully human antibodies for malignant pleural mesothelioma targeting.2020https://dx.doi.org/10.3390/cancers12040915
EmbaseImmunotherapy for mesothelioma: A critical review of current clinical trials and future perspectives.2020https://dx.doi.org/10.21037/tlcr.2019.11.23
EmbaseEmerging avenues in immunotherapy for the management of malignant pleural mesothelioma.2021https://dx.doi.org/10.1186/s12890-021-01513-7
EmbaseOncological frontiers in the treatment of malignant pleural mesothelioma.2021https://dx.doi.org/10.3390/jcm10112290
EmbasePD-1/PD-L1 Checkpoint Inhibitor Immunotherapy for Malignant Pleural Mesothelioma: Case Series and Literature Review.2021https://dx.doi.org/10.1016/j.cllc.2020.05.012
EmbaseTreatment of unresectable malignant pleural mesothelioma in 2021: Emerging standards in immunotherapy.2021https://dx.doi.org/10.20517/2394-4722.2021.97
Dimensions AIResearch Progress of Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma2021https://doi.org/10.3779/j.issn.1009-3419.2021.102.18
EmbaseCurrent status and progress in immunotherapy for malignant pleural mesothelioma.2022https://dx.doi.org/10.1002/cdt3.18
EmbaseImmunotherapy approaches for malignant pleural mesothelioma.2022https://dx.doi.org/10.1038/s41571-022-00649-7
Dimensions AIGenomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma2023https://doi.org/10.1158/2159-8290.cd-22-0886
Dimensions AIImmunotherapy of mesothelioma: the evolving change of a long-standing therapeutic dream2024https://doi.org/10.3389/fimmu.2023.1333661
N.B. These documents automatically identified may not have been verified by the study sponsor.