A phase 2 trial of durvalumab with first line chemotherapy in mesothelioma with a safety run in.
- Conditions
- Malignant Pleural Mesothelioma (MPM).Cancer - Lung - Mesothelioma
- Registration Number
- ACTRN12616001170415
- Lead Sponsor
- niversity of Sydney
- Brief Summary
DREAM: a phase 2 trial of DuRvalumab with first line chEmotherApy in Mesothelioma This is a summary of the final results of DREAM . What was the trial about? The standard, proven treatment for advanced mesothelioma is chemotherapy. Treatment with immune checkpoint inhibitors, drugs that activate the body’s immune system to attack some types of cancer, has been shown to improve survival in people with advanced cancers of the lung, kidney, skin, and other organs. DREAM was designed to determine the possible benefits of combining an immune checkpoint inhibitor called durvalumab with standard chemotherapy in people with advanced mesothelioma. All the people who took part in the DREAM trial (participants) were treated with this combination of durvalumab and standard chemotherapy. What did the trial show? The trial showed that the combination of durvalumab and standard chemotherapy was safe and had promising effects against mesothelioma. Scans showed control of mesothelioma for 6 months or longer in 31 of the 54 participants in the trial, which was higher than the 25 participants expected with chemotherapy alone. How will the results help patients and doctors in future? Following these promising results, our research team is working together with researchers in the USA to open and complete a larger trial that will directly compare the combination standard chemotherapy plus durvalumab versus standard chemotherapy without durvalumab in over 400 people with mesothelioma. Where can I find out more about the trial? More details about the trial are available on website at https://ctc.usyd.edu.au/our-work/research-divisions/cancer/cancer-divisions/lung-cancers/closed/dream/
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 54
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.
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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression free survival at 6 months (PFS6) according to mRECIST for MPM.[ 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 Measures
Name Time Method