Study of Durvalumab or Placebo in Patients with Non-small Cell Lung Cancer (Stage II-III) who’s has residual disease after surgery and chemotherapy.
- Conditions
- Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
- Registration Number
- CTRI/2021/01/030611
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Informed consent
1 Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICFs and in this protocol.
2 Provision of signed and dated, written informed consent form prior to any mandatory study-specific procedures, sampling, and analyses.
i. ICF1 must be signed and dated prior to initiation of the first screening and surveillance activities.
ii. ICF2a must be signed and dated prior to initiation of the second screening activities and randomization.
iii. ICF2b must be signed and dated prior to initiation of the study-specific observation period and procedures.
3 Provision of signed and dated written optional genetic informed consent prior to collection of the optional sample for genetic analysis. This consent should be signed at the time of second screening. This optional sample and analyses are separate from the mandatory genetic testing consent included in ICF1.
4 Age =18 years at the time of screening.
5 Male and/or female.
6 Histologically confirmed NSCLC with resectable stage II-III disease (according to IASLC Staging Manual in Thoracic Oncology v8.0) who have undergone curative intent therapy (complete resection of the primary tumor ± neoadjuvant and/or adjuvant therapy) per SoC. Select stage IIIB (ie, T3N2 or T4N2) patients will be eligible, provided they are upstaged to T3N2 or T4N2 based on confirmed pathology after surgery. Patients who are staged as T3N2 or T4N2 prior to surgery are not eligible.
7 A contrast-enhanced CT/MRI scan of the chest and abdomen (including liver and adrenal glands) along with brain MRI (preferred) or brain CT with IV contrast 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 (computerized tomography) within the 6 weeks prior to surgery in order to rule out detectable extrathoracic, extracranial metastasis and to assess for potential mediastinal lymph node involvement prior to surgery.
8 Complete resection of the primary NSCLC is mandatory. Invasive (pre-operative or intraoperative) exploration of hilar and mediastinal lymph nodes must have been performed to confirm primary tumor nodal status (prior to or after surgery). 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.
9 Patients should have completed (or be undergoing) curative intent therapy (surgery ± neoadjuvant and/or adjuvant therapy; adjuvant therapy can include PORT) with exceptions noted below:
i. Patients who discontinue chemotherapy and/or PORT for toxicity prior to completion of all planned therapy are eligible.
ii. Patients who have not received any neoadjuvant and/or adjuvant chemotherapy, and meet all other eligibility criteria, may be eligible under the following circumstances:
iii. All patients who are eligible for adjuvant chemotherapy MUST be offered adjuvant chemotherapy.
iv. The patient has declined adjuvant chemotherapy, and in the opinion of the Investigator, this is the patient s final decision after receiving appropriate information and adequate time
Diagnostic assessments
1EGFR and/or ALK mutant as assessed either from the tumor biopsy taken prior to surgery or the resected tumor tissue. Testing must be performed using a well-validated, local regulatory-approved test. EGFR/ALK may be tested centrally if local testing is unavailable.
2Mixed small cell and NSCLC histology.
3Require 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.
4Baseline imaging demonstrating unequivocal evidence of RECIST 1.1-defined disease recurrence or evidence of clinical recurrence outside of imaging prior to randomization. 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.
Medical conditions
5History of allogeneic organ or bone marrow transplantation.
6Non-leukocyte-depleted whole blood transfusion within 120 days of genetic sample collection.
7Active 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
8Uncontrolled 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.
9History 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
iii. Adequately treated carcinoma-in-situ without evidence of disease
10History of active primary immunodeficiency
11Active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (HBV; known positive HBV surface antigen [HBsAg] result), hepatitis C (HCV), or human immunodeficiency virus infection (positive HIV 1/2
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the efficacy of durvalumab compared to <br/ ><br>placebo as measured by DFS in the PD-L1 TC=1% <br/ ><br>analysis set <br/ ><br>Timepoint: To assess the efficacy of durvalumab compared to <br/ ><br>placebo as measured by DFS in the PD-L1 TC=1% <br/ ><br>analysis set. 5 years <br/ ><br>
- Secondary Outcome Measures
Name Time Method