Randomized Phase II, 2-arm Study of Immunomodulation with Atezolizumab concomitant with High Dose Radiation (SBRT) Versus SBRT Alone in Patients with Oligometastatic Sarcomas

Phase 1

• Conditions: Soft tissue sarcoma; MedDRA version: 20.0 Level: PT Classification code 10075333 Term: Soft tissue sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004239-35-FR
• Lead Sponsor: Centre Antoine Lacassagne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-05
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 103

Inclusion Criteria

•Histologically proven STS (leiomyosarcomas uterine/extra-uterine, liposarcomas, undifferentiated sarcomas), any grade. A diagnosis confirmation by the RREPS network is preferable but not mandatory.
•Progressive disease according to RECIST 1.1 criteria,
•Metastatic disease (1-5 synchronous macroscopic metastases by chest and abdominopelvic CT, maximal cumulated diameter 6 cm); any anatomic site
•First or second metastatic line
•Be = 18 years of age on day of signing informed consent.
•Have a performance status of 0 or 1 on the ECOG Performance Scale.
•Have at least one lesion evaluable by RECIST 1.1 for irradiation with a size of < 5 cm.
•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 (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. All screening labs should be performed within 15 days of treatment initiation.
•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.
•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.
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 subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 33

Exclusion Criteria

•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.
•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.
•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.
•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.
•Have had previous radical radiation to any tumor site within 4 weeks prior to randomization
•Have had previous ablative treatment within 4 weeks prior to randomization (radiofrequency, surgery)
•Has a tumor within 5 mm of the spinal cord (owing to rare reported cases of flare-up after initiation of immunotherapy)
•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.
•Has an active autoimmune disease requiring systemic treatment within the past 3 months 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.
•Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
•Has an active infection requiring systemic therapy.
•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.
•Has known psychiatric or substance-abuse disorders that would interfere with cooperation with the requirements of the trial.
•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.
•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 checkpoi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified