Table 1 Main inclusion and exclusion criteria of the trial
Inclusion criteria ➢ Histologically proved, metastatic or unresectable locally advanced recurrent SCCA, ➢ Age ≥ 18 years, ➢ ECOG-PS of 0 or 1, ➢ Signed written informed consent. Exclusion Criteria Non-eligibility to clinical trials: ➢ Previous received chemotherapy for metastatic disease, ➢ Previous received cisplatin, except for concomitant CRT, ➢ Previous chemotherapy taxanes or another spindle poison, ➢ Previous received anti-tumour immunotherapy (HPV vaccination is allowed), ➢ Previous radiotherapy within 28 days of randomization (14 days if radiotherapy of bone metastases), ➢ Diagnosis of additional malignancy within 3 years prior to randomization with the exception for curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer, ➢ Any medical or psychiatric condition of disease, which would make the patients inappropriate for entry into this study, ➢ Current participation in a study of an investigational agent or in the period of exclusion, ➢ Pregnancy, breast-feeding, or absence/refusal of adequate contraception for fertile patients, Non-eligibility to chemotherapy: ➢ Inadequate organ functions: uncontrolled cardiac condition, known cardiac failure, unstable coronaropathy, respiratory failure, and Chronic Obstructive Pulmonary Disease (COPD), ➢ Diabetes with vascular or neurovascular complications, ➢ Pre-existent peripheral neuropathy, ➢ HIV-positive with CD4+ count under 400 cells/mm3, ➢ Active hepatitis B or C virus (HBV or HCV) infection, ➢ Active tuberculosis, ➢ Concomitant treatment with CYP3A4 inhibitor like ritonavir, indinavir, or ketoconazole, etc. (Replacement by another drug before randomization, whenever is possible, is allowed), ➢ Known hypersensitivity or contraindication to any of the study chemotherapy drugs (taxanes, cisplatin, 5-fluorouracil), ➢ Uncontrolled infection or another life-risk condition, ➢ Known hearing impairment that contraindicates cisplatin administration, ➢ Inadequate laboratory values: creatinine clearance (CrCl by Modification of Diet in Renal Disease [MDRD] formula) < 60 ml/min, neutrophil count < 1500 /mm3, platelets < 100,000/mm3, bilirubin 2.5 x upper limit of normal (ULN), aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 x ULN or 5 x ULN with liver metastasis, ➢ Patient with known dihydropyridine dehydrogenase (DPD) deficiency or history. Non-eligible to immunotherapy: ➢ Any immunosuppressive therapy (i.e. corticosteroids > 10 mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy, ➢ Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed, ➢ Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, ➢ Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study, ➢ Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study, ➢ Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: o Rash must cover < 10% of body surface area, o Disease is well controlled at baseline and requires only low-potency topical corticosteroids, o No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months, ➢ Prior allogeneic bone marrow transplantation or prior solid organ transplantation, ➢ Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed, ➢ Previously received an anti-PD1, anti-PDL1, or anti-CTLA4 agent, ➢ Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of atezolizumab formulation, ➢ History of colorectal inflammatory disease, ➢ History of idiopathic or secondary pulmonary fibrosis (history of radiation pneumonitis in the radiation field fibrosis is permitted), or evidence of active pneumonitis requiring a systemic treatment with 28 days before the planned start of study therapy, ➢ Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study, ➢ Severe infection within 4 weeks prior to initiation of study treatment. |