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).
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Administration of L-TC (300 mg) as an IV perfusion, daily before each radiotion session
HFRT : 30 Gy in 5 fractions of 6 Gy. 1 fraction per day, 5 days per week.
CGFL
Dijon, France
ICANS
Strasbourg, France
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.
Time frame: At surgery (Between 4 and 8 weeks after the end of radiotherapy)
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: at 4 months after surgery, and at 12, 18, 24, 36 and 60 months
Evaluation of tumour necrosis
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Proportion of patient whom tumor has pathologic necrosis on histologic examination
Time frame: 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
Time frame: at screening and before surgery
Proportion of patients with R0 resection
Number of patients with R0 resection on the number of enrolled patients
Time frame: At 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: at the inclusion (baseline) and every 4 months the two first years and then every 6 months the next three years