RANDOMIZED STUDY OF ATEZOLIZUMAB (MPDL3280A, ANTI PD-L1 ANTIBODY) IN COMBINATION WITH CARBOPLATIN + PACLITAXEL+BEVACIZUMAB COMPARED WITH PEMETREXED + CISPLATIN OR CARBOPLATIN WITH STAGE IV NON-SQUAMOUS NON-SMALL CELL LUNG CANCER
- Conditions
- Neoplasms
- Registration Number
- KCT0004043
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 228
Patients may be eligible if they have cytotoxic chemotherapy naive, Stage IV, non-squamous NSCLC with activating EGFR mutation or ALK translocation.
Patients must meet all of the following criteria to be eligible for study entry:
•Signed Informed Consent Form
•Male or female, 18 years of age or older
•ECOG performance status of 0 or 1
•Histologically or cytologically confirmed, Stage IV non-squamous NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system, 8th edition).
Patients with tumors of mixed histology (i.e., squamous and non-squamous) are eligible if the major histological component appears to be non-squamous.
•As the stage IV non-squamous NSCLC treatment, no prior cytotoxic treatment is allowed and the patients treated with below tyrosine kinase inhibitor prior to the enrollment
Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more EGFR TKIs, such as erlotinib, gefitinib, osimertinib or another EGFR tyrosine kinase inhibitor (TKI) appropriate for the treatment of EGFR mutant NSCLC.
If the patients have identified T790M mutation after 1st or 2nd generation EGFR TKI failure, the patient must be treated with the second line 3rd generation EGFR TKI treatment, such as osimertinib, before the study participation.
Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene.
Patients with unknown EGFR and/or ALK status require test results at screening. ALK and/or EGFR may be assessed locally or at a main investigator laboratory.
Inoperable stage III non-squamous NSCLC treatment, no prior cytotoxic treatment is allowed and the patients treated with below tyrosine kinase inhibitor prior to the enrollment
•Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy.
•Patients with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
No ongoing requirement for corticosteroids as therapy for CNS disease
No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization
No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
Patients with new asymptomatic CNS metastases detected at the screening scan may be eligible without the need for an additional radiation therapy and/or surgery for CNS metastases by investigator’s decision.
•Patients who are available to provide tissue from previously obtained archival tumor tissue or tissue obtained from a biopsy at screening for the PD-L1 test (in case, if patient cannot provides any slides, the enrollment can still be considered with individual discussion with the principal investigator
•Biopsy and blood sample requirement are as follows for the Whole exome and transcriptome sequencing:
A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in p
Patients who meet any of the criteria below will be excluded from study entry.
Cancer-Specific Exclusions
•Active or untreated symptomatic CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
•Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization
•Leptomeningeal disease
•Uncontrolled tumor-related pain
Patients requiring pain medication must be on a stable regimen at study entry.
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to randomization.
•Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX®) are allowed.
•Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL)
Patients who are receiving denosumab prior to randomization must be willing and eligible to receive a bisphosphonate instead while in the study.
•Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5 year OS ? 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
General Medical Exclusions
•Women who are pregnant, lactating, or intending to become pregnant during the study
•History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
•Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
•History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study.
Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen are eligible for this study
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
Rash must cover less than 10% of body surface area (BSA).
Disease is well controlled at baseline and only requiring low-pote
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method progression-free survival, PFS
- Secondary Outcome Measures
Name Time Method overall survival(OS), objective response rate(ORR), duration of response(DOR)