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

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.

Conditions

• Sarcoma,Soft Tissue

Interventions

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

Sponsors & Collaborators

• Roche Pharma AG

  collaborator INDUSTRY

• Centre Leon Berard

  lead OTHER

Principal Investigators

• Jean-Yves BLAY, MD · Centre Leon Berard

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-08-01

Primary Completion

2026-12-30

Completion

2026-12-30

Countries

• France
• United Kingdom

Study Locations