The Total Neoadjuvant Therapy for Soft Tissue Sarcoma of the Extremities

NCT06593899 | Recruiting Phase 2 DMC

• 1 other identifier: IRGHO-STS23
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

For localized soft tissue sarcomas (STS) of the extremities, limb-sparing or conservative surgery with perioperative radiotherapy (RT) is the standard of care. However, several challenges persist. Notably, there are exceedingly high rates of distant metastatic recurrence even after surgical resection and RT, and conventional fractionated radiotherapy has a prolonged duration (5-6 weeks). With advancements in RT technology, the gradual expansion of hypofractionated radiotherapy regimens enables significantly shorter treatment durations. Promising recent reports on 1-week hypofractionated RT regimens, such as the 5X5 Gy RT regimens, have demonstrated reasonable local control and acceptable toxicity in resectable STS.Addressing the challenge of distant metastasis, previous studies have indicated that AI regimens are expected to eliminate micrometastases and improve survival in patients with STS at a high risk of distant relapse. Therefore, the goal of this clinical trial is to investigate whether hypofractionated RT combined with a sequential chemotherapy（AI regimens）can enhance short-term treatment efficacy for extremity STS patients without compromising local control rates and increasing related toxicities

Conditions

Soft Tissue Sarcomas

Outcome Measures

Primary Outcomes (1)

• The proportion of EORTC-STBSG classifications A-C (less than 10% tumour residual)

  Surgery

Secondary Outcomes (3)

• Postoperative wound complications

  3 months

• Overall survival

  24 months after treatment completion

• Local control

  24 months after treatment completion

Study Arms (1)

Hypofractionated Radiotherapy

EXPERIMENTAL

The patients in the study underwent a 1-week course of hypofractionated radiotherapy. Following the completion of radiotherapy, chemotherapy with the AI regimen (doxorubicin + ifosfamide) was initiated one week later. The AI regimen chemotherapy was administered for a duration of 9 weeks. Subsequently, surgery was scheduled to commence 1-2 weeks after the completion of chemotherapy.

Radiation: Hypofractionated Radiotherapy; Drug: 3 cycles of AI

Interventions

Hypofractionated Radiotherapy RADIATION

Hypofractionated radiotherapy Preoperative hypofractionated 5x5 Gy radiotherapy (5 consecutive days) prescribed on planned target volume

Hypofractionated Radiotherapy

3 cycles of AI DRUG

Three courses of doxorubicin and ifosfamide (AI, doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm with prophylactic mesna)

Hypofractionated Radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary soft tissue sarcoma of the extremities, with one of the following characteristics: high grade, ≥5cm or deep tumor, the need for neoadjuvant radiotherapy was determined after multidisciplinary consultation.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• Age 18-75 years old.
• Histologic diagnosis of soft tissue sarcoma.
• Can tolerate radiotherapy and AI regimen treatment.
• The function of major organs is normal.

You may not qualify if:

• There were no patients with gross tumors after unplanned mass resection in another hospital.
• Patients with other comorbidities cannot use AI chemotherapy: drug allergy, active bleeding, ulcers, intestinal perforation, intestinal obstruction, uncontrollable hypertension, grade III-IV cardiac insufficiency (NYHA standards), severe liver and renal insufficiency ( Level IV) etc.
• New malignant tumors within 5 years (except cervical carcinoma in situ or early cutaneous basal cell carcinoma).
• Pathological types: nonpleomorphic rhabdomyosarcoma, Ewing sarcoma.
• Soft tissue sarcoma curable by simple expansion.
• Previous history of radiotherapy to the same site.
• Combined with distant metastasis (M1) or lymph node metastasis (N1).
• Have other severe medical comorbidities that preclude surgery or participation in the study.
• Previous exposure to chemotherapy.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead

Study Sites (1)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

Related Publications (4)

• Blay JY, Honore C, Stoeckle E, Meeus P, Jafari M, Gouin F, Anract P, Ferron G, Rochwerger A, Ropars M, Carrere S, Marchal F, Sirveaux F, Di Marco A, Le Nail LR, Guiramand J, Vaz G, Machiavello JC, Marco O, Causeret S, Gimbergues P, Fiorenza F, Chaigneau L, Guillemin F, Guilloit JM, Dujardin F, Spano JP, Ruzic JC, Michot A, Soibinet P, Bompas E, Chevreau C, Duffaud F, Rios M, Perrin C, Firmin N, Bertucci F, Le Pechoux C, Le Loarer F, Collard O, Karanian-Philippe M, Brahmi M, Dufresne A, Dupre A, Ducimetiere F, Giraud A, Perol D, Toulmonde M, Ray-Coquard I, Italiano A, Le Cesne A, Penel N, Bonvalot S; NETSARC/REPPS/RESOS and French Sarcoma Group-Groupe d'Etude des Tumeurs Osseuses (GSF-GETO) Networks. Surgery in reference centers improves survival of sarcoma patients: a nationwide study. Ann Oncol. 2019 Jul 1;30(7):1143-1153. doi: 10.1093/annonc/mdz124. Erratum In: Ann Oncol. 2019 Aug 1;30(8):1407. doi: 10.1093/annonc/mdz170.

  PMID: 31081028 BACKGROUND

• Gronchi A, Stacchiotti S, Verderio P, Ferrari S, Martin Broto J, Lopez-Pousa A, Llombart-Bosch A, Dei Tos AP, Collini P, Jurado JC, De Paoli A, Donati DM, Poveda A, Quagliuolo V, Comandone A, Grignani G, Morosi C, Messina A, De Sanctis R, Bottelli S, Palassini E, Casali PG, Picci P. Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. Ann Oncol. 2016 Dec;27(12):2283-2288. doi: 10.1093/annonc/mdw430. Epub 2016 Oct 11.

  PMID: 27733375 BACKGROUND

• Kalbasi A, Kamrava M, Chu FI, Telesca D, Van Dams R, Yang Y, Ruan D, Nelson SD, Dry SM, Hernandez J, Chmielowski B, Singh AS, Bukata SV, Bernthal NM, Steinberg ML, Weidhaas JB, Eilber FC. A Phase II Trial of 5-Day Neoadjuvant Radiotherapy for Patients with High-Risk Primary Soft Tissue Sarcoma. Clin Cancer Res. 2020 Apr 15;26(8):1829-1836. doi: 10.1158/1078-0432.CCR-19-3524. Epub 2020 Feb 13.

  PMID: 32054730 BACKGROUND

• Gobo Silva ML, Lopes de Mello CA, Aguiar Junior S, D'Almeida Costa F, Stevanato Filho PR, Santoro Bezerra T, Nakagawa SA, Nascimento AG, Werneck da Cunha I, Spencer Sobreira Batista RM, Nicolau Daher UR, Da Cruz Formiga MN, Germano JN, Catin Kupper BE, De Assis Pellizzon AC, Lopes A. Neoadjuvant hypofractionated radiotherapy and chemotherapy for extremity soft tissue sarcomas: Safety, feasibility, and early oncologic outcomes of a phase 2 trial. Radiother Oncol. 2021 Jun;159:161-167. doi: 10.1016/j.radonc.2021.03.033. Epub 2021 Mar 31.

  PMID: 33798613 BACKGROUND

MeSH Terms

Conditions

Sarcoma

Interventions

Radiation Dose Hypofractionation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Yong Yang, Doctor

  Director of the radiotherapy department

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong Yang, Doctor

CONTACT

18813019084; dr_yangyong1983@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DR.

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: May 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 19, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)