Study of Durvalumab or Placebo given along with Standard Chemotherapy in Patients with Non-small Cell Lung Cancer (Stage II-III) who’s tumor has been removed through surgery
- Conditions
- Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
- Registration Number
- CTRI/2020/09/027739
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
Informed consent
Criteria and procedures initiated with the signing of ICF1
1ICF1 must be signed and dated prior to any study procedures and prior to the planned surgical resection of the primary NSCLC, with the exception noted below.
i. Exception: Patients will be permitted to sign ICF1 after surgery. In this case, a post surgical whole blood sample and resected tumor tissue must be collected as soon as possible for development of the personalized panel. The plasma sample to determine MRD status must still be collected between Weeks 3 and 4 post-surgery, even if creation of the personalized panel for MRD detection is delayed. Only patients identified as MRD+ based on the post-surgery plasma sample may be randomized in the study, provided all additional inclusion and none of the exclusion criteria are met.
ii. Patients randomized to the MRD- cohort must have had a plasma sample collected prior to surgery and will not be eligible for the study if they signed ICF1 after surgery. Patients will not be excluded from randomization based on the results of the pre-surgical sample.
Age
2Age =18 years at the time of screening.
Sex
3Male and/or female.
Type of patient and disease characteristics
4. Individuals who have diagnosis of histologically confirmed NSCLC with resectable (stage II-III) disease, 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 as T3N2 or T4N2 prior to surgery are not eligible.
The following criteria must be met prior to surgery or at the time of the surgery:
5A contrast-enhanced CT/MRI scan of the chest and abdomen (including liver and adrenal glands) 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 in order to rule out detectable extrathoracic, extracranial metastasis and to assess for potential mediastinal lymph node involvement prior to surgery. 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, algorithm to follow for primary mediastinal staging when PET-CT is available). Brain MRI (preferred) or brain CT with IV contrast is required for complete staging of the tumor. Imaging should occur within 6 weeks prior to surgery.
Complete resection of the primary NSCLC is mandatory. The primary tumor must be deemed resectable by a multidisciplinary evaluation that must include a thoracic surgeon certified or trained according to local standards and who performs lung cancer surgery as a significant part of their practice. Surgical resection of the primary NSCLC can occur by open thoracotomy or by video-assisted thoracic surgery (VATS) and resection can be achieved by segmentectomy, lobectomy, sleeve resection, bilobectomy, or pneumonectomy. Patients undergoing wedge resection are not eligible for this study.
At a minimum, the following parameters should be met for a tumor to be declared completely resected:
(a)The surgeon performing the resection should remove all gross disease by t
Diagnostic assessments
1Post-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.
2EGFR-mutant and/or ALK-translocation as assessed either from the tumor biopsy taken prior to surgery (preferred) or the resected tumor tissue (if biopsy was not evaluable). If a pre surgery biopsy is not available, testing will be conducted as soon as possible post surgery on the resected tumor tissue while the personalized panel is in development; patients will still be allowed to continue with study procedures while testing is ongoing but will be excluded from randomization if their resected tumor tissue tests positive for EGFR mutations and/or ALK translocations. Testing must be performed using a well validated, local regulatory approved test. EGFR/ALK may be tested centrally if local testing is unavailable.
3Mixed small cell and NSCLC histology.
4Require 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.
5Patients who are candidates to undergo only wedge resections.
Medical conditions
6History of allogeneic organ or bone marrow transplantation.
7Non-leukocyte-depleted whole blood transfusion within 120 days of genetic sample collection.
8Active 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:
i. Patients with vitiligo or alopecia
ii. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
iii.Any chronic skin condition that does not require systemic therapy
iv.Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
v.Patients with celiac disease controlled by diet alone
9Uncontrolled 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.
10History of another primary malignancy, except for
i. Malignancy treated with curative intent and with no known active disease =5 years before the first dose of IP and of low potential risk for recurrence
ii.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the efficacy of durvalumab plus SoC chemotherapy compared to placebo plus SoC chemotherapy as measured by DFS in MRD positive patientsTimepoint: To assess the efficacy of durvalumab plus SoC chemotherapy compared to placebo plus SoC chemotherapy as measured by DFS in MRD positive patients - 4.5 years
- Secondary Outcome Measures
Name Time Method