MERMAID-1
- Conditions
- This is a Phase III, randomized, parallel-arm, placebo controlled, double blind, multicenter study assessing the efficacy and safety of durvalumab versus placebo following SoC chemotherapy in patients with completely resected stage II-III NSCLC who are MRD+ post surgery
- Registration Number
- JPRN-jRCT2080225282
- Lead Sponsor
- AstraZeneca KK
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 31
Patients must be capable of giving signed informed consent, which includes a mandatory genetic informed consent and compliance with the requirements and restrictions listed in the informed consent forms (ICFs) and in this protocol. Provision of signed and dated, written ICFs must occur prior to any mandatory study-specific procedures, sampling, and analyses. In addition to ICF1 and ICF2, patients will provide signed and dated written optional genetic informed consent prior to collection of a sample for optional genetic analysis at the time of second screening (Table 2). This is different from the genetic samples and testing covered by ICF1, which are mandatory for participation in this study. Criteria and procedures initiated with the signing of ICF1
1. ICF1 must be signed and dated prior to any study procedures and prior to the planned surgical resection of the primary NSCLC, with the exceptions noted below. This consent will cover the study-specific first screening procedures outlined in Table 1. Exception: Patients will be permitted to sign ICF1 up to Week 3 (Day 21) postsurgery. Patients identified after Week 3 post-surgery but prior to Week 5 (Day 35) post-surgery may be allowed to sign ICF1 depending on the outcome of the discussion with the study physician. In these cases, a whole blood sample and resected tumor tissue must be collected and sent to the diagnostic lab as soon as possible after ICF1 is signed for development of the personalized panel. A plasma sample must still be collected at Week 3-5 (Day 21-35) post-surgery, even if creation of the personalized panel for MRD detection is delayed.
2. Age 18 years or more at the time of screening. 3. Male and/or female. Type of patient and disease characteristics 4. Individuals who have diagnosis of histologically confirmed NSCLC (WHO 2015 classification) with resectable (stage II-III) disease (according to IASLC Staging Manual in Thoracic Oncology v8.0). Select (ie, T3N2 or T4N2) stage IIIB patients will be eligible, provided that they are upstaged to T3N2 or T4N2 based on confirmed pathology. Patients who are staged asT3N2 or T4N2 prior to surgery are not eligible.
5. A contrast-enhanced CT or MRI scan of the chest must have been done for surgical planning prior to surgery. It is recommended that patients undergo combined FDG-PET (18F-Fluoro-deoxyglucose positron emission tomography) and CT scan (contrastenhanced or low-dose CT component) in order to rule out detectable extrathoracic, extracranial metastasis and to assess for potential mediastinal lymph node involvement prior to surgery. In the absence of pre-operative FDG-PET CT imaging, pre-operative contrast-enhanced CT imaging or MRI scan must cover liver and adrenal glands. If only CT is available, or FDG-PET reveals suspicious lymph node mediastinal involvement, it is recommended that invasive pre-operative mediastinal staging is performed according to the algorithm of the European Society of Thoracic Surgeons guidelines (algorithm to follow for primary mediastinal staging if only pre-operative CT is available [De Leyn et al 2007], algorithm to follow for primary mediastinal staging when PET-CT is available [De Leyn et al 2014]). It is preferred that imaging occurs within 6 weeks prior to surgery. Brain MRI (preferred) or brain CT with IV contrast is required for complete staging of the tumor. 6. Complete resection of the primary NSCLC is mandatory. The primary tumor must be deemed resectable by a multidisciplinary evaluat
Diagnostic assessments
1. Post-operative imaging demonstrating unequivocal evidence of disease recurrence or tissue biopsy-proven disease recurrence. In the event of lymphadenopathy on imaging that would lead to exclusion, histopathological confirmation of lymph node metastasis should be obtained prior to excluding a patient from the study. If pathological confirmation of lymph-node metastasis is not technically feasible and imaging appearance are deemed unequivocal for relapse, the patient will be excluded.
2. EGFR-mutant and/or ALK-translocation-positive, as assessed either from a pre-surgical biopsy sample (preferred) or the resected tumor tissue (if biopsy was not evaluable or available). Any of the following scenarios are acceptable for this study:
Where EGFR/ALK results are obtained from a pre-surgical tissue biopsy as part of standard local practice, the patient must be confirmed EGFR/ALK wild-type prior to enrolling in the study.
Results obtained from testing the patient's primary tumor tissue during screening for another AstraZeneca study may be used in this study.
Results from local testing of a pre-surgical biopsy. All local EGFR/ALK testing performed locally must be performed using a well-validated, local regulatory-approved test. EGFR/ALK may be tested centrally if local testing is unavailable. Patients will still be allowed to continue with first screening procedures while testing is ongoing but will not be able to continue into second screening if their tumor tests positive for EGFR mutations and/or ALK translocations.
3. Mixed small cell and NSCLC histology.
4. Require re-resection or are deemed to have unresectable NSCLC by a multidisciplinary evaluation that must include a thoracic surgeon who performs lung cancer surgery as a significant part of their practice.
5. Patients who are candidates to undergo only wedge resections. Medical conditions
6. History of allogeneic organ or bone marrow transplantation.
7. Non-leukocyte-depleted whole blood transfusion within 120 days of genetic sample collection. Note: This exclusion criterion only relates to whole blood and does not include other blood products (eg, packed red blood cells).
8. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
- Patients with celiac disease controlled by diet alone
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>-
- Secondary Outcome Measures
Name Time Method safety<br>efficacy<br>exploratory<br>pharmacokinetics<br>-