Clinical trial NCT06476704: Study of Preoperative RAdiation Therapy With Concomitant Liposomal Transcrocetin (L-TC) in Soft tISsue Sarcomas
Official title: Phase 2 Study of Preoperative RAdiation Therapy With Concomitant Liposomal Transcrocetin (L-TC) in Soft tISsue Sarcomas
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Sarcoma
Keywords: hypofractionated radiotherapy
soft tissue sarcoma
hypoxia
liposomal transcrocetin
neo-adjuvant
Lead sponsor: Institut de cancérologie Strasbourg Europe
Sponsor class: OTHER
Collaborators: name: LEAF4Life, Inc.
First posted: 2024-06-26
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of the efficacy of the L-TC treatment in combination with preoperative hypofractionated radiotherapy (HFRT)
timeFrame: At surgery (Between 4 and 8 weeks after the end of radiotherapy)
Secondary outcomes:
measure: Evaluation of the acute tolerance o f L-TC
timeFrame: Up to day 5 (every day during the treatment)
measure: Evaluation of the late tolerance o f L-TC
timeFrame: Up to day 28 after the end of treatment.
measure: Evaluation of the acute tolerance of radiotherapy
timeFrame: Up to day 5 (every day during the treatment)
measure: Evaluation of the late tolerance of radiotherapy
timeFrame: at 4 months after surgery, and at 12, 18, 24, 36 and 60 months
measure: Evaluation of tumour necrosis
timeFrame: At surgery (Between 4 and 8 weeks after the end of radiotherapy)
measure: Evaluation of the radiological response
timeFrame: at screening and before surgery
measure: Proportion of patients with R0 resection
timeFrame: At surgery
measure: Evaluation of the Local Progression-Free Survival (L-PFS)
timeFrame: at 12, 24, 36 and 60 months.
measure: Evaluation of the Distant Progression-Free Survival (D-PFS)
timeFrame: at 12, 24, 36 and 60 months.
measure: Evaluation of the Overall Survival (OS)
timeFrame: at 12, 24, 36 and 60 months
measure: Evaluation of the Quality of Life (QoL)
timeFrame: at the inclusion (baseline) and every 4 months the two first years and then every 6 months the next three years
Other outcomes:
Locations:
city: Dijon
country: France
facility: CGFL
city: Strasbourg
country: France
facility: ICANS
Study officials:
affiliation: Institut de cancérologie Strasbourg Europe
name: Isabelle CHAMBRELANT, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de cancérologie Strasbourg Europe
name: Georges NOEL, MD, PhD
role: STUDY_CHAIR
References: