Study of Preoperative RAdiation Therapy With Concomitant Liposomal Transcrocetin (L-TC) in Soft tISsue Sarcomas (PRACTISS)

Phase 2 Study of Preoperative RAdiation Therapy With Concomitant Liposomal Transcrocetin (L-TC) in Soft tISsue Sarcomas

This is phase II randomized, multicenter study of treatment with L-TC and preoperative HFRT in patients who were aged 18 years or older with documented localised or locally advanced soft-tissue sarcoma of the extremity.

Eligible patients will be randomly assigned 2:1 to receive a preoperative HFRT alone (Arm A) or L-TC with preoperative HFRT (Arm B).

Study Overview

• Status: Not yet recruiting
• Conditions: Sarcoma
• Intervention / Treatment: Drug: Administration of L-TC; Radiation: HFRT alone

Detailed Description

This is a non-comparative phase II trial (comparison is made regarding a reference, not 2 between 2 proportions). Considering the wide confidence interval retrieved in literature regarding pCR value with HFRT, pCR value used in the sample size calculation and taken from the literature must be included in the 95% CI of the pCR from the control group.

The PRACTISS trial aims to improve treatment outcomes for patients with extremity STS by incorporating Liposomal Transcrocetin (L-TC) with Hypofractionated Radiotherapy (HFRT). L-TC is designed to enhance tumor oxygenation, addressing hypoxia-a significant factor contributing to radioresistance. By reoxygenating tumor cells, L-TC may improve radiosensitivity, increasing the efficacy of radiotherapy and leading to higher rates of pathological complete response (pCR) before surgery. Achieving a higher pCR is associated with better long-term outcomes and reduced recurrence rates. Additionally, the use of HFRT reduces the overall treatment schedule compared to conventional radiotherapy, minimizing the treatment burden for patients and potentially improving their quality of life while maintaining treatment effectiveness.

L-TC 300 mg QD, administered as intravenous infusion over 90 minutes, at a fixed dose of 300 mg daily before each HFRT fraction, for a total of 5 days corresponding to the planned five daily HFRT fractions. The intravenous infusion should start 120 minutes before each HFRT fraction. Radiotherapy is scheduled to coincide with the plasma peak, which occurs approximately 2 hours after the start of the infusion

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Manon VOEGELIN; Phone Number: +33 368339523; Email: promotion-rc@icans.eu

Study Locations

• France
  • Dijon, France
    • CGFL
    • Contact: Gilles TRUC; Phone Number: 33380737518; Email: gtruc@cgfl.fr
  • Strasbourg, France
    • ICANS
    • Contact: Georges NOEL; Phone Number: 33368339523; Email: promotion-rc@icans.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Localized or locally advanced soft tissue sarcoma of extremity proven by biopsy histological grade 2 and 3.
• Pathological expert proof-reading in reference centers
• HFRT and surgery planned (regardless the potential inclusion in this trial) as decided in a multidisciplinary tumor board, in reference centre (European Society for Medical Oncology (ESMO) guideline 2021)
• R0 surgery is feasible, in reference centers
• Pre-biopsy MRI available
• Performance status of 0-2 and life expectancy of at least 6 months

Exclusion Criteria:

• Patient who cannot undergo MRI
• Patients with localized or locally advanced soft tissue sarcoma of extremity proven by biopsy with histological grade 1
• Previous radiation in the area
• Woman who is pregnant or breastfeeding
• Soft tissue sarcoma developed in irradiated area.
• Patients with myxoid liposarcoma, embryonal or alveolar rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, angiosarcoma, primitive neuroectodermal tumor, desmoid-type fibromatosis, or dermatofibrosarcoma protuberans
• Patient with metastatic disease, other concomitant cancer or history of cancer treated and controlled within the previous 3 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionated radiotherapy + Liposomal Transcorcetin (L-TC); L-TC as an IV infusion over 90 minutes at a fixed dose of 300 mg daily before each HFRT fraction, for a total of 5 days corresponding to the planned five daily HFRT fractions. The intravenous infusion should begin 2 hours before each HFRT fraction. Radiotherapy is scheduled to coincide with the plasma peak, which occurs approximately 2 hours after the start of the infusion. + HFRT treatment will be administered in control group as 30 Gy in 5 fractions of 6 Gy. 1 fraction per day, 5 days per week.	Drug: Administration of L-TC; Administration of L-TC (300 mg) as an IV perfusion, daily before each radiotion session
Active Comparator: Hypofractionated radiotherapy alone; HFRT treatment will be administered in control group as 30 Gy in 5 fractions of 6 Gy. 1 fraction per day, 5 days per week.	Radiation: HFRT alone; HFRT : 30 Gy in 5 fractions of 6 Gy. 1 fraction per day, 5 days per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the efficacy of the L-TC treatment in combination with preoperative hypofractionated radiotherapy (HFRT)	Pathological complete response rate (pCR): defined as the presence of < 10% residual malignant viable cells.	At surgery (Between 4 and 8 weeks after the end of radiotherapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with R0 resection	Number of patients with R0 resection on the number of enrolled patients	At surgery
Evaluation of the acute tolerance o f L-TC	Toxicities and biological analysis before each injection of L-TC and before surgery, described by type and grade, using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 classification	Up to day 5 (every day during the treatment)
Evaluation of the late tolerance o f L-TC	Toxicities and biological analysis before each injection of L-TC and before surgery, described by type and grade, using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 classification	Up to day 28 after the end of treatment.
Evaluation of the acute tolerance of radiotherapy	Global tolerance (radiotherapy toxicities (oedema, radiodermatitis, fibrosis, bone fracture) and laboratory abnormalities) at each physician consultation for radiotherapy and at follow-up, using the CTCAE v.5.0 classification	Up to day 5 (every day during the treatment)
Evaluation of the late tolerance of radiotherapy	Global tolerance (radiotherapy toxicities (oedema, radiodermatitis, fibrosis, bone fracture) and laboratory abnormalities) at each physician consultation for radiotherapy and at follow-up, using the CTCAE v.5.0 classification	at 4 months after surgery, and at 12, 18, 24, 36 and 60 months
Evaluation of tumour necrosis	Proportion of patient whom tumor has pathologic necrosis on histologic examination	At surgery (Between 4 and 8 weeks after the end of radiotherapy)
Evaluation of the radiological response	Proportion of patients with a complete or partial radiological response (according to RECIST 1.1) evaluated on MRI	at screening and before surgery
Evaluation of the Local Progression-Free Survival (L-PFS)	L-PFS will be defined as the length of time from the date of diagnostic by biopsy to the date of local relapse on MRI. L-PFS will be determined in median and rate	at 12, 24, 36 and 60 months.
Evaluation of the Distant Progression-Free Survival (D-PFS)	D-PFS will be defined as the length of time from the date of diagnostic by biopsy to the date of distant relapse on scanner. D-PFS will be determined in median and rate	at 12, 24, 36 and 60 months.
Evaluation of the Overall Survival (OS)	OS will be defined as the length of time from the date of diagnostic by biopsy to the date of death, whatever the cause. Patients will be censored on the last news date. OS will be determined in median and rate	at 12, 24, 36 and 60 months
Evaluation of the Quality of Life (QoL)	Use of the European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire (QLQ-C30)	at the inclusion (baseline) and every 4 months the two first years and then every 6 months the next three years

Collaborators and Investigators

• Sponsor: Centre Paul Strauss
• Collaborators: LEAF4Life, Inc.
• Investigators: Principal Investigator: Isabelle CHAMBRELANT, MD, Institut de cancérologie Strasbourg Europe; Study Chair: Georges NOEL, MD, PhD, Institut de cancérologie Strasbourg Europe

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 15, 2028
• Study Completion (Estimated): June 1, 2033

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: hypoxia; hypofractionated radiotherapy; neo-adjuvant; soft tissue sarcoma; liposomal transcrocetin
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Signs and Symptoms, Respiratory; Neoplasms, Connective and Soft Tissue; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypoxia; Sarcoma
• Other Study ID Numbers: 2020-016; 2024-515668-30-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes