localised and operable soft tissue sarcomas MedDRA version: 20.0 Level: PT Classification code 10039491 Term: Sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: TECENTRIQ
Product Name: Atezolizumab
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Tecentriq
Other descriptive name: RO5541267
Concentration unit: mg milligram(s)
Concen
Sponsors
Centre Léon Bérard
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1.Male or female patients aged = 18 years at time of inform consent signature. I2.Histologically confirmed soft tissue sarcoma including liposarcoma, leiomyosarcoma, myxofibrosarcoma, UPS, angiosarcoma, all translocation sarcoma except Ewing, rhabdomyosarcoma (RMS), and myxoid liposarcoma (LPS). I3.Soft tissue sarcoma suitable for neoadjuvant RT and amenable to surgery with curative intent (high-grade non-metastatic tumors, intermediate and low-grade tumors greater than 5 cm). Note: Patients with local relapsing disease amenable to surgery are eligible. I4.Presence of at least one tumor lesion with a diameter =10 mm, visible by medical imaging and accessible to percutaneous or endoscopic sampling that permit core needle biopsy without unacceptable risk and suitable for retrieval of a minimum of three, but ideally 4, cores using a biopsy needle of at least 16-gauge. I5.Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 (Appendix 1). I6.Adequate end organs and bone marrow functions as defined below according to lab tests performed within 7 days before W1D1: Bone marrow (without transfusion within 2 weeks before W1D1): o Hemoglobin = 9.0 g/dL, oAbsolute neutrophil count = 1.5 x 109/L, oPlatelets = 100 x 109/L, oLymphocyte count = 0.5 x 109/L. Renal function: o Serum creatinine clearance = 30 mL/min/1.73m2 (MDRD or CKD-EPI formula - Appendix 3) Hepatic function o Serum bilirubin 28 days, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, Live attenuated vaccines > 30 days, Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. Major surgical procedure, open biopsy (excluding skin cancer resection and screening tumor biopsy), or significant traumatic injury > 14 days (the wound must have healed), Any approved or investigational anti-cancer therapy, including chemotherapy, hormonal therapy or targeted therapy > 21 days, Systemic immunostimulatory agents > 28 days or five half-lives of the drug, whichever is longer, Oral or IV antibiotics > 14 days. I8.Women of child-bearing potential must have a negative serum pregnancy test within 7 days before randomisation and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 5 months after the last dose of atezolizumab (See Appendix 5). I9.Fertile men must agree to use an effective method of birth control during the study and for up to 5 months after the last dose of atezolizumab. I10.Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient shoul
Exclusion criteria
Exclusion criteria: E1.Patients with evidence of metastatic disease, defined by the presence of any of the followings: Lesions that are discontinuous from the primary tumor, Lesions that are not regional lymph nodes, Lesions that do not share a body cavity with the primary tumor, Evidence by medical imagining (eg CT-scan) of metastatic disease. E2.Patients with history of severe allergic or other hypersensitivity reactions to: Chimeric or humanized antibodies or fusion proteins, Biopharmaceuticals produced in Chinese hamster ovary cells, or Any component of the atezolizumab formulation. E3.Patients using or requirement to use while on the study of any not permitted concomitant medications : Any approved anti-cancer systemic treatment including chemotherapy, hormonotherapy, biological therapy, immunotherapy other than atezolizumab, Any investigational agents, Live vaccines. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines, and are not allowed during the study active period, Traditional herbal medicines since the ingredients of many herbal medicines are not fully studied and their use may result in unanticipated drug-drug interactions that may cause or confound assessment of toxicity, Immunostimulatory agents, including but not limited to IFN-a, IFN-?, or IL-2, during the entire study. These agents, in combination with atezolizumab, could potentially increase the risk for autoimmune conditions. In addition, all patients (including those who discontinue the study early) should not receive other immunostimulatory agents for 10 weeks after the last dose of atezolizumab, Immunosuppressive medications, including but not limited to cyclophosphamide, azathioprine, methotrexate, and thalidomide. These agents could potentially alter the activity and the safety of atezolizumab. Systemic corticosteroids and anti-TNF-a agents may attenuate potential beneficial immunologic effects of treatment with atezolizumab but may be administered to manage irAE (See Safety Plan). If feasible, alternatives to these agents should be considered. E4.Patients with a malignancy other than STS within 5 years prior to randomisation with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated in situ carcinoma of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal in situ carcinoma treated surgically with curative intent). E5.Patients with severe infections within 4 weeks prior to randomisation including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia. E6.Patients with 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. E7.Patients with active B or C hepatitis infection. E8.Patients with active tuberculosis. E9.Patients with ongoing toxicities (Grade =1 according to CTCAE V4.03) from previous therapie
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the clinical impact of PD-L1 neutralisation with or without radiotherapy versus radiotherapy alone based on the rate of pathological response defined by at least =80% pathologic necrosis on the surgery specimen. ;Secondary Objective: To evaluate the clinical activity of the proposed strategy based on : - Rate of patients with complete or near-complete pathologic response defined as = 95% tumor necrosis. - Rate of patients with at least = 50% tumor necrosis . - Percentage of residual viable cells. - Objective Response Rate as RECIST v1.1. - Tumor volume change - Quality of resection and amputation rate. - Local Recurrence Rate (LRR) at 1 year post-surgery - Time To Relapse (TTR) - Disease Free Survival (DFS) To assess the impact of study treatments on immune cell infiltration such as T cells (including but not limited to GmzB+/CD8+ T-cell, CD3+), B cells (CD20, IgG), and Treg (FOXP3) on pre (de novo tumor biopsy at baseline) and post-treatment (surgery specimen) by immunofluorescence. To assess the safety and tolerability of proposed strategies in terms of Adverse Event (AE), Serious Adverse Events (SAEs), AESI and SUSARs. ;Primary end point(s): rate of pathological response defined by at least =80% pathologic necrosis on the surgery specimen. ;Timepoint(s) of evaluation of this end point: post-surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of patients with complete or near-complete pathologic response defined as = 95% tumor necrosis. - Rate of patients with at least = 50% tumor necrosis . - Percentage of residual viable cells. - Objective Response Rate as RECIST v1.1. - Tumor volume change - Quality of resection and amputation rate. - Local Recurrence Rate (LRR) at 1 year post-surgery - Time To Relapse (TTR) - Disease Free Survival (DFS) Evolution of number of T cells (including but not limited to GmzB+/CD8+ T-cell, CD3+), B cells (CD20, IgG), and Treg (FOXP3) on pre (de novo tumor biopsy at baseline) and post-treatment (surgery specimen) by immunofluorescence. Incidene of Adverse Event (AE), Serious Adverse Events (SAEs), AESI and SUSARs. ;Timepoint(s) of evaluation of this end point: 12 months post-surgery | — |
Countries
France
Contacts
Public ContactDRCI
Centre Léon bérard
Outcome results
None listed