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

NCT03474094 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: RT-Immune (ET16-132)
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 6

Brief 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

Keywords

Clinical Trial; randomized; phase II; atezolizumab; PD-L1

Outcome Measures

Primary Outcomes (1)

• Pathological impact of PD-L1 neutralisation (by atezolizumab) with or without radiotherapy versus radiotherapy alone in operable localised STS

  Rate of pathological response (defined by at least 80°% of necrosis on surgery specimens) following PDL1 neutralisation with atezolizumab +/- radiotherapy versus RT alone

  11 weeks

Secondary Outcomes (14)

• Rate of patients with complete or near-complete pathologic response

  11 weeks

• Rate of patients with at least 50% of necrosis

  11 weeks

• Percentage of residual viable cells

  11 weeks

• Objective Response Rate (ORR)

  11 weeks

• Tumor volume change

  11 weeks

Study Arms (3)

pre-operative radiotherapy and atezolizumab

EXPERIMENTAL

Pre-operative radiotherapy followed by 2 cycles of atezolizumab then surgery

Combination Product: Pre-operative radiotherapy followed by 2 cycles of atezolizumab then surgery

pre-operative atezolizumab and post-operative radiotherapy

EXPERIMENTAL

2 cycles of atezolizumab followed by surgery then post-operative radiotherapy

Combination Product: 2 cycles of atezolizumab followed by surgery then post-operative radiotherapy

pre-operative radiotherapy and post-operative atezolizumab

ACTIVE COMPARATOR

Pre-operative radiotherapy then surgery followed by 2 cycles of atezolizumab

Combination Product: Pre-operative radiotherapy followed by surgery then 2 cycles of atezolizumab.

Interventions

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

pre-operative radiotherapy and post-operative atezolizumab

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 atezolizumab and post-operative radiotherapy

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

pre-operative radiotherapy and atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 18 years at time of inform consent signature.
• Histologically confirmed soft tissue sarcoma including liposarcoma, leiomyosarcoma, myxofibrosarcoma, UPS, angiosarcoma, all translocation sarcoma except Ewing, rhabdomyosarcoma (RMS), and myxoid liposarcoma (LPS).
• Soft tissue sarcoma suitable for neoadjuvant RT and amenable to surgery with curative intent (high-grade non-metastatic tumors, intermediate and low-grade tumors greater than 5 cm).
• Note: Patients with local relapsing disease amenable to surgery are eligible.
• Presence of at least one tumor lesion with a diameter ≥10 mm, visible by medical imaging and accessible to percutaneous or endoscopic sampling that permit core needle biopsy without unacceptable risk and suitable for retrieval of a minimum of three, but ideally 4, cores using a biopsy needle of at least 16-gauge.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 (Appendix 4).
• Adequate end organs and bone marrow functions as defined below according to lab tests performed within 7 days before W1D1:
• Bone marrow (without transfusion within 2 weeks before W1D1):
• Hemoglobin ≥ 9.0 g/dL,
• Absolute neutrophil count ≥ 1.5 x 109/L,
• Platelets ≥ 100 x 109/L,
• Lymphocyte count ≥ 0.5 x 109/L.
• Renal function:
• Serum creatinine clearance ≥ 30 mL/min/1.73m2 (MDRD or CKD-EPI formula - Appendix 3)
• Hepatic function

You may not qualify if:

• Patients with evidence of metastatic disease, defined by the presence of any of the followings:
• Lesions that are discontinuous from the primary tumor,
• Lesions that are not regional lymph nodes,
• Lesions that do not share a body cavity with the primary tumor,
• Evidence by medical imagining (eg CT-scan) of metastatic disease.
• Patients with history of severe allergic or other hypersensitivity reactions to:
• Chimeric or humanized antibodies or fusion proteins,
• Biopharmaceuticals produced in Chinese hamster ovary cells, or
• Any component of the atezolizumab formulation.
• Patients using or requirement to use while on the study of any not permitted concomitant medications :
• Any approved anti-cancer systemic treatment including chemotherapy, hormonotherapy, biological therapy, immunotherapy other than atezolizumab,
• Any investigational agents,
• Live vaccines. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines, and are not allowed during the study active period,
• Traditional herbal medicines since the ingredients of many herbal medicines are not fully studied and their use may result in unanticipated drug-drug interactions that may cause or confound assessment of toxicity,
• Immunostimulatory agents, including but not limited to IFN-α, IFN-γ, or IL-2, during the entire study. These agents, in combination with atezolizumab, could potentially increase the risk for autoimmune conditions. In addition, all patients (including those who discontinue the study early) should not receive other immunostimulatory agents for 10 weeks after the last dose of atezolizumab,

Sponsors & Collaborators

• Centre Leon Berard: lead
• Roche Pharma AG: collaborator

Study Sites (6)

Institut Bergonie

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Royal Marsden Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Jean-Yves BLAY, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 22, 2018
• Study Start: August 1, 2018
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

GB (1); FR (5)