Mesothelioma Malignant Advanced Clinical Trial
— DREAM3ROfficial title:
DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial
The purpose of this study is to investigate the effectiveness of durvalumab in combination
with standard chemotherapy for mesothelioma. All participants in the study will receive
standard first-line chemotherapy for mesothelioma. 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 to attack cancer cells. Research has shown that
durvalumab can slow tumour growth and shrink tumours in some people with cancer. Previous
studies of combining durvalumab and chemotherapy showed that this combination is active in
advanced mesothelioma.
This international study is being led jointly by the University of Sydney in Australia, and
the Pr Eastern Cooperative Oncology Group (PrECOG) in the USA. The study plans to enrol 480
participants from hospitals throughout Australia, New Zealand and the USA.
| Status | Not yet recruiting |
| Enrollment | 480 |
| Est. completion date | June 2024 |
| Est. primary completion date | June 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Adults (18 years or over) with a histological diagnosis of malignant pleural mesothelioma that is not amenable to curative surgical resection. 2. Measurable disease as per modified RECIST 1.1 (mRECIST 1.1) criteria for assessment of response in malignant pleural mesothelioma (Appendix 1 - Modified RECIST 1.1 Criteria for Assessment of Response in Malignant Pleural Mesothelioma (MPM) and imaging manual), without prior radiotherapy to these sites. 3. Body weight >30kg. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 2 - ECOG Performance Status Scales) 5. Tumour tissue (Formalin-Fixed Paraffin-Embedded (FFPE)) available from diagnostic biopsy for PD-L1 testing and other correlative biomarker testing at a central laboratory. 6. Life expectancy of at least 12 weeks. 7. 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 109/L - Platelets = 100 x 109/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 (use Cockcroft-Gault formula as per Appendix 3 - Cockcroft-Gault formula) 6. 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. 7. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments. 8. 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 (double if required) barrier method of contraception if they are sexually active with a woman of child bearing potential (see Appendix 4 - Acceptable birth control methods). 9. 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. (see Appendix 4 - Acceptable birth control methods). Exclusion Criteria: 1. Prior chemotherapy or other systemic anti-cancer or immunotherapy for MPM. 2. Diagnosis on cytology or fine needle aspiration biopsy only. 3. 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 4. 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. 5. Participants with symptomatic or uncontrolled brain metastases or leptomeningeal disease are excluded. 6. Prior therapy with an anti-PD-1, anti-PD-L1 (including durvalumab), anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways. 7. Current treatment or treatment within the last 12 months with any investigational anti-cancer products. 8. 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. 9. 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. 10. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study drug. 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. 11. Hearing loss or peripheral neuropathy considered by the investigators to contraindicate cisplatin administration. 12. History of allergy or hypersensitivity to investigational product, cisplatin, pemetrexed or any excipient. 13. 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. 14. 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. 15. Known history of primary immunodeficiency, allogeneic organ transplant, pneumonitis or active tuberculosis. 16. Receipt of live attenuated vaccination within 30 days prior to enrolment or within 30 days of receiving durvalumab. 17. Specific comorbidities or conditions or concomitant medications which may interact with the investigational product(s). 18. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results. 19. 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. |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| University of Sydney | AstraZeneca, Australasian Lung Cancer Trials Group, PrECOG, LLC. |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Tertiary/Correlative Measures | Translational research studies aim to identify biomarkers that may be prognostic and/or predictive of response to treatment, safety and resistance to treatment (associations of biomarkers with clinical outcomes). | Blood samples at baseline, at the start of cycle 2 (each cycle is 21 days) and at the start of cycle 3. Tumor tissue from diagnostic biopsy, and if biopsy is clinically indicated during/after treatment (within 24 months after randomization) (optional). | |
| Primary | Overall survival | It is defined as the time from randomization to the date of death due to any cause. Patients who are alive at the time of the final analysis or who have become lost to follow-up will be censored at their last known alive date. | Minimum follow up is 24 months after randomisation | |
| Secondary | Progression Free Survival | Progression Free Survival (PFS) is defined as the interval from date of randomization to the date of first evidence of disease progression or death, whichever occurs first | Minimum follow up is 24 months after randomisation | |
| Secondary | Objective Tumour Response Rate | 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 Response Criteria in Solid Tumors (RECIST) 1.1 criteria for assessment of response in malignant pleural mesothelioma | Minimum follow up is 24 months after randomization | |
| Secondary | Rates of adverse events | Adverse events (AEs) graded according to NCI CTCAE version 5.0. The number and percentage of participants who experience AEs will be tabulated according to CTCAE term/category and grade. | 90 days after last dose of durvalumab or 30 days after last dose of chemotherapy, whichever is longer | |
| Secondary | Health-Related Quality of Life: QLQ-C30 | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Importance of quality of life issues are assessed using a four-point scale (1 = not at all, 4 = very much). | 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 randomization) | |
| Secondary | Health-Related Quality of Life: QLQ-LC29 | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module (QLQ-LC29). Importance of quality of life issues are assessed using a four-point scale (1 = not at all, 4 = very much). | 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 randomization) | |
| Secondary | Health-Related Quality of Life: EQ-5D-5L | Euro-Quality of Life (EuroQoL) 5 dimension 5 level (EQ-5D-5L) Questionnaire, comprising 5 questions with a score from 1 (no problem) to 5 (extreme problem) and a visual analogue scale from 0 (worst) to 100 (best). | 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 randomization) | |
| Secondary | Health care resource usage costs | Hospitalization costs calculated by applying Australian unit costs to Australian Refined Diagnostic Related Groups (AR DRG) costs for hospitalizations. | Minimum follow up is 24 months after randomisation | |
| Secondary | Health care resource usage costs | Scheduled costs for visits to health professionals, collected for Australian participants via the Medical Benefits Schedule (MBS). | Minimum follow up is 24 months after randomisation | |
| Secondary | Health care resource usage costs | Scheduled costs for medications, collected for Australian participants via the Pharmaceutical Benefits Schedule (PBS). | Minimum follow up is 24 months after randomisation |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT05188859 -
First Line Sintilimab Combined With Anlotinib and Platinum Doublet Chemotherapy in Malignant Pleural Mesothelioma
|
Phase 2 |