Atezolizumab for Soft tissue sarcoma

Inclusion criteria

• {"criterion_text":"-Histologically proven STS (uterine/extra-uterine leiomyosarcomas, liposarcomas, undifferentiated sarcomas), any grade. A diagnosis confirmation by the RREPS network is preferable but not mandatory."}
• {"criterion_text":"-Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy,"}
• {"criterion_text":"-Patient willing and able to provide written informed consent/assent for the trial,"}
• {"criterion_text":"-Patient affiliated with a health insurance system,"}
• {"criterion_text":"-Progressive disease according to RECIST 1.1 criteria"}
• {"criterion_text":"-Metastatic disease (1-5 synchronous macroscopic metastases by chest and abdominopelvic CT, maximal cumulated diameter 10 cm); any anatomic site"}
• {"criterion_text":"-Have at least one measurable lesion according to RECIST 1.1 criteria for irradiation with a size < 5 cm,"}
• {"criterion_text":"-First or second metastatic line"}
• {"criterion_text":"-Be ≥ 18 years of age on day of signing informed consent"}
• {"criterion_text":"-Have a performance status of 0 or 1 on the ECOG Performance Scale"}
• {"criterion_text":"-Demonstrate adequate organ function: - Absolute neutrophil count (ANC) ≥1,500 /mcL; - Platelets ≥100,000 / mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L; - Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance with MDRD equation (GFR can also be used in place of creatinine or CrCl) ≥50 mL/min for subject with creatinine levels > 1.5 X institutional ULN; - Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN; - AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases."}
• {"criterion_text":"-Surgical ablation (or other ablative methods such as thermal ablative methods) remains possible if needed before SBRT, at least 4 weeks before randomization and provided that at least one lesion needs to be treated by SBRT,"}

Exclusion criteria

• {"criterion_text":"-Is currently participating in, or has participated in, a study of an investigational agent or using an investigational device within 4 weeks prior to randomization"}
• {"criterion_text":"-Has an active autoimmune disease requiring systemic treatment within the past 3 months prior randomization or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study,"}
• {"criterion_text":"-Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis,"}
• {"criterion_text":"-Has an active infection requiring systemic therapy,"}
• {"criterion_text":"-Has received a live vaccine within 30 days prior to the first dose of trial treatment,"}
• {"criterion_text":"-Has a tumor within 5 mm of the spinal cord (owing to rare reported cases of flare-up after initiation of immunotherapy),"}
• {"criterion_text":"-Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy,"}
• {"criterion_text":"-Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies),"}
• {"criterion_text":"-Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA [qualitative] is detected),"}
• {"criterion_text":"-Has known Hypersensitivity to Atezolizumab or to any of the excipients (L-histidine, Glacial acetic acid,Sucrose,Polysorbate 20),"}
• {"criterion_text":"-Has known liver disease that could increase susceptibility to or exacerbate the impact of any potential hepatotoxicity of Atezolizumab,"}
• {"criterion_text":"-Has had prior chemotherapy or targeted small molecule therapy within 4 weeks prior to randomization or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study). If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy,"}
• {"criterion_text":"-Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator,"}
• {"criterion_text":"-Has known psychiatric or substance-abuse disorders that would interfere with cooperation with the requirements of the trial,"}
• {"criterion_text":"-Is pregnant or breastfeeding or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment,"}
• {"criterion_text":"-Is a vulnerable persons as defined by article L1121-5 - 8: 1/Pregnant women, women in labour or breast-feeding mothers, persons deprived of their freedom by judicial or administrative decision, persons hospitalized without their consent by virtue of articles L. 3212-1 and L. 3213-1 and who are not subject to the provisions of article L. 1121-8. 2/Persons admitted to a social or health facility for reasons other than research. 3/ Adults subject to a legal protection order or unable to give their consent"}
• {"criterion_text":"-Have had previous radical radiation to any tumor site within 4 weeks prior to randomization"}
• {"criterion_text":"-Have had previous ablative treatment within 4 weeks prior to randomization (radiofrequency, surgery),"}
• {"criterion_text":"-Has had major surgery or major blood transfusions (>3 packed cells) in the past 3 months prior randomization,"}
• {"criterion_text":"-Has had a prior monoclonal antibody within 4 weeks prior to randomization or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier,"}
• {"criterion_text":"-Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways),"}
• {"criterion_text":"-Receives IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses),"}
• {"criterion_text":"-Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment,"}

Primary endpoints

• {"endpoint_text":"-The rate of progression-free survival (PFS) at 6 months.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"-PFS by immune response criteria defined as the time between the date of D1 of treatment and the date of progression or the date of death or the date of last news","definition_or_measurement_approach":"Defined as the time between date of D1 of treatment and date of progression or date of death or date of last news."}
• {"endpoint_text":"-Objective response rate defined according to RECIST criteria version 1.1","definition_or_measurement_approach":"Defined according to RECIST criteria version 1.1."}
• {"endpoint_text":"-Rate of progression-free survival (PFS) at 6 months as defined in the primary endpoint by line of treatment and by histology","definition_or_measurement_approach":"PFS rate at 6 months stratified by line of treatment and histology as per primary endpoint."}
• {"endpoint_text":"-Toxicity will be evaluated according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Toxicities of all grades will be analyzed and then the analysis will be focused on grades ≥ 3","definition_or_measurement_approach":"Toxicity graded using NCI-CTC version 5.0; analyses on all grades and specifically grades ≥ 3."}
• {"endpoint_text":"-Overall Survival defined as the time between the date of D1 of treatment and the date of death or the date of last news for those still alive at the end of the follow-up","definition_or_measurement_approach":"Defined as time from D1 of treatment to date of death or date of last contact."}
• {"endpoint_text":"-Quality of life will be measured using standard EORTC QLQc30","definition_or_measurement_approach":"Measured using the EORTC QLQ-C30 questionnaire."}
• {"endpoint_text":"-The cost of the treatment will be calculated on the basis of the length of hospitalization in days.","definition_or_measurement_approach":"Cost calculated based on length of hospitalization in days."}
• {"endpoint_text":"-Rate of PET-CT scan performed at inclusion.","definition_or_measurement_approach":"Proportion of patients with PET-CT performed at inclusion."}
• {"endpoint_text":"-Impact of biomarkers (including PD1/PDL1 immunostaining in tumor and microenvironment, CRP, albumin, neutrophils/lymphocytes, mutational load at baseline and ctDNA analyses at baseline, 6 months and relapse) on PFS as previously described","definition_or_measurement_approach":"Assessment of specified biomarkers (PD1/PDL1 IHC, CRP, albumin, N/L ratio, mutational load, ctDNA at baseline/6 months/relapse) and their association with PFS."}
• {"endpoint_text":"-Validation of the predictive models.","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

15-10-2024

Latest Decision Or Authorization Date

23-12-2025

Processing Time Days

434

Number Of Sites

17

Number Of Participants

103

Primary sponsor

Full Name

Centre Antoine Lacassagne

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France