Advanced Non-small cell lung cancer (NSCLC) with rare histological subtypes MedDRA version: 21.1 Level: LLT Classification code 10064049 Term: Lung adenocarcinoma metastatic System Organ Class: 100000004864
Conditions
Sponsors
GRUPPO ONCOLOGICO ITALIANO DI RICERCA CLINICA (GOIRC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Locally advanced, relapsed or metastatic non-small cell lung cancer – stage IIIB/IV. • Histologically confirmed diagnosis of non-small cell lung cancer with rare histological subtype, according to World Health Organization (WHO) 2015 classification. Histologic subtype variants to be enrolled into the study include: large cell neuroendocrine carcinoma (LCNEC); • Availability of tumor sample (material obtained from core-biopsy or surgical specimen) for central pathology revision is mandatory. • Availability of a formalin-fixed, paraffin-embedded tumor block or 7-10 unstained tumor slides suitable for PD-L1 expression assessment is mandatory. The assessment of PD-L1 expression will be performed by using both SP-142 and SP-263 antibody assays. The collection of tumor sample should be performed before patients are enrolled into the study . • Male and female and = 18 years of age. • Life expectancy = 12 weeks. • Progressive disease after or during at least one previous standard chemotherapy line. • Measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1); clear radiological evidence of disease progression after previous treatment has to be documented. • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2. • Patients with treated brain metastases with stable lesions for at least 2 weeks either off steroids or on a stable dose or decreasing dose of steroids (= 10 mg prednisone or equivalent daily) will be enrolled. Radiotherapy must have been completed a minimum of 14 days prior to registration, and patients must have recovered from adverse events (AEs) related to radiotherapy to < grade 1 (except alopecia). • For Females: must be postmenopausal for at least 1 year before the screening visit, or are surgically sterile or not sexually active. Women of childbearing potential (WOCBP) must use 2 effective methods of contraception with a failure rate of less than1% per year, during the entire study treatment period and for a period of 5 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. WOCBP must have a negative serum pregnancy test during the screening period. • Adequate haematological function defined by white blood cell count =2,500/mm3 with absolute neutrophil count =1,500/mm3, platelet count =100,000/mm3 and haemoglobin =9g/dL. • Adequate hepatic function defined by a total bilirubin = 1.5 x the upper limit of normal (ULN) range (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL), serum alanine aminotransferase and aspartate aminotransferase = 2.5 x ULN. • Adequate renal function defined by a serum creatinine = 1.5 x ULN or an estimated creatinine clearance of = 30 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft-Gault formula). • Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria. • Recovered (i.e., = Grade 1 toxicity) from effects of prior anticancer therapy, except alopecia. • Ability to comply with protocol requirements. •The patient is able to provide written informed consent before performance. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subject
Exclusion criteria
Exclusion criteria: • Prior treatment with Atezolizumab or any other immunotherapy agents (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways). • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation. • Concurrent anticancer treatment, immune therapy, or cytokine therapy, except for erythropoietin. • Major surgery for any reason within 4 weeks (or 2 weeks for minor surgery) from registration and/or if the subject has not fully recovery from the surgery within 4 weeks of registration. • Subjects receiving immunosuppressive agents such as steroids for any reason should be tapered off these drugs before initiation of the trial treatment. Corticosteroid therapy with a dose = 10 mg prednisone or equivalent will be allowed. Note: o Subjects receiving bisphosphonates or denosumab are eligible provided treatment was initiated at least 14 days before first dose of trial treatment o Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be =10 mg per day of equivalent prednisone. • Persisting toxicity related to prior therapy of grade >1 according to National Cancer Institute - Common Terminology Criteria Adverse Event (NCI-CTCAE) v. 4.03. • Known severe hypersensitivity reactions to chimeric or monoclonal antibodies, fusion proteins (grade =3 NCI-CTCAE v. 4.03). • Patients with untreated, symptomatic and/or progressive brain metastases, or with carcinomatous meningitis. • History of autoimmune disease. • Any medical condition requiring a systemic corticosteroid treatment at doses >10 mg prednisone per day or equivalent or other immunosuppressive therapies. • Other concurrent neoplasms. • Prior organ transplantation, including allogenic stem-cell transplantation. •Any medical condition, within 6 months before receiving the first dose of study drug, considered relevant by Investigator. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. Patients who present particular clinical conditions or relevant comorbidity may be enrolled into the study upon discussion with the Study Coordinator. • Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). • Any positive test for hepatitis C virus at screening •Any positive test indicating active hepatitis B infection; patients with positive total HBcAb test followed by a negative HBV-DNA test at screening could be enrolled, according to hepatologist counselling • Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before the first dose of study drug. • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. • Active tuberculosis. • Pregnancy or breastfeeding. • Vaccination within 4 weeks of the first dose of atezolizumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated flue vaccines) • Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site person
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess antitumor activity and safety of atezolizumab as treatment in a cohort of pretreated, advanced non-small cell lung cancer (NSCLC) patients with rare histological subtypes.;Secondary Objective: To evaluate safety and efficacy of atezolizumab in subjects with advanced NSCLC with rare histological subtypes who relapsed during or after at least one previous standard chemotherapy line.;Primary end point(s): The primary end-point is disease control rate (DCR) that will be considered as the sum of complete responses (CRs), partial responses (PRs) and stable disease (SD), based on the Investigator’s assessment according to standard RECIST 1.1 criteria. Data will be reported as percentage of CRs, PRs, SD and progressive disease (PD). Patients with no tumor assessment after baseline will be classified as non-responders. At the time of first tumor assessment, subjects treated with atezolizumab will be permitted to continue investigational treatment beyond initial RECIST v 1.1 defined PD, assessed by the Investigator, in presence of the following criteria: Investigator- assessed clinical benefit, no rapid disease progression (defined as =2-fold increase of tumor growth rate) [1], good tolerance of study drug, stable performance status. The decision to continue treatment beyond initial Investigator-assessed progression should be discussed with Study Coordinators and documented in the study records. The assessment of clinical benefit should be balanced by clinical judgment as to whether the subject is clinically deteriorating and unlikely to receive any benefit from continued treatment with atezolizumab. If the Investigator feels that the atezolizumab subject continues to achieve clinical benefit by continuing treatment, the subject should remain on the trial. A radiographic reassessment will be performed within 6 weeks of initial Investigator- assessed progression to determine whether there has been a decrease in the tumor size or continued PD. For the | — |
Countries
Italy
Contacts
Public ContactResponsabile Scientifico
Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)
Outcome results
None listed