NCT03474094

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

A European, Multicenter, Randomized, Open-label, Phase II Trial Aiming to Assess the Clinical and Biological Activity of an Anti-PD-L1 (Atezolizumab) in Operable Localised Soft Tissue Sarcomas Patients to be Treated With Radiotherapy

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 62 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This trial is a European, multicenter, open-label, randomized, Phase II trial using a pick-the-winner design aiming to the clinical and biological activity of anti-PD-L1 (atezolizumab) in a population of operable localised soft tissue sarcomas (STS) patients to be treated with radiotherapy. Following inform consent signature and validation of eligibility criteria, patients will be randomized (1:1:1) into one of the 3 study arms: * Arm A: Pre-operative radiotherapy followed by 2 cycles of atezolizumab then surgery * Arm B: 2 cycles of atezolizumab followed by surgery then post-operative radiotherapy * Arm C: Pre-operative radiotherapy followed by surgery then 2 cycles of atezolizumab. The sequence of treatment is different between the study arms, but the regimen of study treatments are the same. All randomized patients will received: * The conventionally fractionated radiotherapy regimen of 2 Gy, 5 days a week up to a total dose of 50 Gy over 5 weeks. Radiotherapy will be either pre-(Arms A and C) or post-(Arm B) operative. * Two cycles of atezolizumab (1200mg, IV, Q3W) * Surgery will be performed as per institutional practice. Randomisation will be stratified according to histological subtypes as follows * Group 1: Leiomyosarcoma \[LMS\], Undifferentiated Pleomorphic Sarcoma \[UPS\], Liposarcoma \[LPS\], myxofibrosarcoma, angiosarcoma versus * Group 2: all translocation sarcoma except Ewing, rhabdomyosarcoma RMS and myxoid LPS. Following this sequence of treatment, all patients will be followed-up 2 weeks after the end of the treatment period then W18, W24 (=M6) then every 3 months until disease relapse, death, loss to follow-up. The minimal follow-up will be 1 year for the last randomized patient. During the study period, the following tumor samples will be also collected for all randomized patients: * A de novo tumor biopsy before study treatment start (pre-treatment tumor sample) * A fragment of the surgery specimen.

Conditions

• Sarcoma,Soft Tissue

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Pre-operative radiotherapy followed by 2 cycles of atezolizumab then surgery	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
COMBINATION_PRODUCT	2 cycles of atezolizumab followed by surgery then post-operative radiotherapy	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.
COMBINATION_PRODUCT	Pre-operative radiotherapy followed by surgery then 2 cycles of atezolizumab.	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

Timeline

• Start date: 2018-08-01
• Primary completion: 2026-12-30
• Completion: 2026-12-30
• First posted: 2018-03-22
• Last updated: 2026-02-10

Locations

6 sites across 2 countries: France, United Kingdom