Clinical and Biological Activity of an Anti-PD-L1 (Atezolizumab) in Operable Localised Soft Tissue Sarcomas Patients to be Treated With Radiotherapy

Sponsor
Centre Leon Berard
Study ID
NCT03474094
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Sarcoma,Soft Tissue

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Pre-operative radiotherapy followed by 2 cycles of atezolizumab then surgery — COMBINATION_PRODUCT
    W1,W2, W3, W4 \& W5: RADIOTHERAPY. A 3-dimensional conformal RT (3D-CRT) with photons ≥ 6MV will be realized based on the acquisition of a CT-scan performed in treatment position. Intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT) and tomotherapy are authorized. W6 and W9: ATEZOLIZUMAB IV INJECTION. 2 injections of 1200 mg of atezolizumab with a 3-week interval W11: SURGERY. Surgery should be performed as per Institutional practice by a surgeon with appropriate training in the treatment of sarcoma. The primary aim of surgery is to completely excise the tumor with a margin of normal tissue commonly accepted as 1 cm soft tissue, or equivalent
  • 2 cycles of atezolizumab followed by surgery then post-operative radiotherapy — COMBINATION_PRODUCT
    W1 and W4: ATEZOLIZUMAB IV INJECTION. 2 injections of 1200 mg of atezolizumab with a 3-week interval W6: SURGERY Surgery should be performed as per Institutional practice by a surgeon with appropriate training in the treatment of sarcoma. The primary aim of surgery is to completely excise the tumor with a margin of normal tissue commonly accepted as 1 cm soft tissue, or equivalent W7, W8, W9, W10 \& W11: RADIOTHERAPY A 3-dimensional conformal RT (3D-CRT) with photons ≥ 6MV will be realized based on the acquisition of a CT-scan performed in treatment position. Intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT) and tomotherapy are authorized.
  • Pre-operative radiotherapy followed by surgery then 2 cycles of atezolizumab. — COMBINATION_PRODUCT
    W1,W2, W3, W4 \& W5: RADIOTHERAPY A 3-dimensional conformal RT (3D-CRT) with photons ≥ 6MV will be realized based on the acquisition of a CT-scan performed in treatment position. Intensity modulated RT (IMRT), volumetric modulated arc therapy (VMAT) and tomotherapy are authorized. W6: SURGERY Surgery should be performed as per Institutional practice by a surgeon with appropriate training in the treatment of sarcoma. The primary aim of surgery is to completely excise the tumor with a margin of normal tissue commonly accepted as 1 cm soft tissue, or equivalent W11 and W14: ATEZOLIZUMAB IV INJECTION. 2 injections of 1200 mg of atezolizumab with a 3-week interval

Study Details

This multicentric, randomised, Phase II trial will use a pick-the-winner design in order to evaluate the clinical and biological activity of atezolizumab when combined with pre-operative or post-operative radiotherapy in STS patients. Following Inform Consent Form (ICF) signature, eligible patients will be randomised (1:1:1) to receive: * Arm A: Radiotherapy followed by atezolizumab then surgery. * Arm B: Atezolizumab followed by surgery then radiotherapy. * Arm C: Radiotherapy then surgery followed by atezolizumab. The sequence of the study treatments is different among the 3 study arms. However, the dose regimens will be the same: * Atezolizumab will be administered to all patients at the dose of 1200mg, by IV injection, for 2 cycles (Q3W). * Radiotherapy will be administered to all patients at the dose of 2Gy/day, 5 days per week, for a total of 5 weeks and 50Gy. * Surgery will be performed as per institutional practice. Randomisation will be stratified according to histological subtypes as follows: Group 1: Liposarcoma (LPS), Undifferentiated Pleomorphic Sarcoma (UPS), Leiomyosarcoma (LMS), myxofibrosarcoma, angiosarcoma versus Group 2: all translocation sarcoma except Ewing, rhabdomyosarcoma (RMS) and myxoid LPS.

Key Dates

Start date
Aug 1, 2018
Status verified
Feb 2026
Primary completion
Dec 30, 2026
Completion
Dec 30, 2026

Study Design

Enrollment
62 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: pre-operative radiotherapy and atezolizumab
    Pre-operative radiotherapy followed by 2 cycles of atezolizumab then surgery
  • Experimental: pre-operative atezolizumab and post-operative radiotherapy
    2 cycles of atezolizumab followed by surgery then post-operative radiotherapy
  • Active Comparator: pre-operative radiotherapy and post-operative atezolizumab
    Pre-operative radiotherapy then surgery followed by 2 cycles of atezolizumab

Primary Outcome Measure

Pathological impact of PD-L1 neutralisation (by atezolizumab) with or without radiotherapy versus radiotherapy alone in operable localised STS [ Time Frame: 11 weeks ]

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