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

Sarcoma,Soft Tissue Clinical Trial

Official title: 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 Recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma,Soft Tissue

• NCT number: NCT03474094
• Study type: Interventional
• Source: Centre Leon Berard
• Contact: Jean-Yves BLAY, MD
• Phone: +33 4 78 78 51 26
• Email: jean-yves.blay@lyon.unicancer.fr
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2018
• Completion date: August 1, 2024