Hypofractionated Radiotherapy With Sequential Chemotherapy in Primary Unresectable or Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall (UN-RESARC)
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|ClinicalTrials.gov Identifier: NCT03651375|
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : June 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Sarcoma Fibrosarcoma Leiomyosarcoma Liposarcoma Myosarcoma Histiocytic Sarcoma Synovial Sarcoma Lymphangiosarcoma Malignant Peripheral Nerve Sheath Tumors Myxofibrosarcoma Myxoid Liposarcoma Undifferentiated Sarcoma Pleomorphic Liposarcoma Undifferentiated Pleomorphic Sarcoma Dedifferentiated Liposarcoma Pleomorphic Rhabdomyosarcoma Malignant Triton Tumor||Drug: Sequential chemotherapy - 3 courses of AI Radiation: Hypofractionated radiotherapy||Phase 2|
There is lack of standard treatment of unresectable and marginally resectable sarcomas. Results of commonly used approaches are unsatisfactory. The addition of neoadjuvant/induction chemotherapy before the irradiation and in the prolonged gap between the end of hypofractionated 5x5 Gy radiotherapy and surgery may allow to obtain the R0 resection rate, high pathological response rate and/or a higher rate of limb-sparing/conservative surgery as well as to increase patients' survival.
Hypofractionation represents a variation of radiotherapy fractionation in which the total dose is divided into fewer fractions with an increased fraction dose. Such treatment may lead to additional biological effects when compared to conventionally fractionated radiotherapy (eg. vascular damage, increased immunogenicity, and antigenicity). The main advantages of hypofractionation are those related to the decreased overall treatment time what is more convenient for both patients and physicians, increased compliance and makes the treatment more cost-effective. Intriguing, such an approach may provide an additional benefit when treating non-radiosensitive tumors with a low alpha/beta ratio (eg. sarcomas).
The basis of the study was a trial conducted by Kosela et al. in our center, which showed that preoperative short 5x5 Gy radiotherapy with immediate surgery is an effective and well-tolerated treatment of resectable sarcomas of extremities or trunk wall.
The rationale of chemotherapy comes for the interim analysis of a multicenter, international EORTC study comparing neoadjuvant systemic approaches in high-risk sarcomas. It was proven that AI regimen, which consists of ifosfamide and anthracyclines allowed to obtain 20% benefit in relapse-free survival and overall survival as compared to pathologically—tailored chemotherapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Hypofractionated 5x5 Gy Radiotherapy With Sequential Doxorubicin and Ifosfamide-based Chemotherapy in Primary Unresectable or Marginally Resectable Soft Tissue Sarcomas of Extremities or Trunk Wall|
|Actual Study Start Date :||February 11, 2017|
|Estimated Primary Completion Date :||September 2019|
|Estimated Study Completion Date :||March 2022|
Experimental: Sequential chemoradiotherapy
1xAI (doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm) + 5x5 Gy radiotherapy + 2xAI + surgery
Drug: Sequential chemotherapy - 3 courses of AI
Three courses of doxorubicin and ifosfamide (AI, doxorubicin 75 mg/sqm and ifosfamide 10 g/sqm with prophylactic mesna), one before radiotherapy and two within the gap between radiotherapy and surgery.
Radiation: Hypofractionated radiotherapy
Preoperative hypofractionated 5x5 Gy radiotherapy (5 consecutive days) prescribed on planned target volume (tumor volume + elective margins + setup/error margin) with a daily image guidance with cone beam-CT-based position verification.
- R0 resection rate [ Time Frame: 24 months ]The rate of micro- and macroscopically radical surgeries.
- Conservative/limb-sparing resection rate [ Time Frame: 24 months ]The rate of limb-sparing or conservative resections vs amputations or no possibility to perform surgery (unresectability).
- Radiological response in diffusion-weighted MRI [ Time Frame: 24 months ]Radiological assessment of tumor change, especially diffusion parameters in DWI-MRI 6 weeks after the end of irradiation, according to the EORTC criteria.
- Pathological response in resected tumors according to EORTC Soft Tissue and Bone Sarcoma Group criteria [ Time Frame: 24 months ]
- Toxicity of planned schedule of therapy according to CTCAE v.4.0 and Clavier-Dindo scale for surgical complications [ Time Frame: 60 months ]The study will be stopped prematurely if the rate of grade 3 skin toxicity >30%.
- 3-years overall survival [ Time Frame: 60 months ]
- 3-years local control rate [ Time Frame: 60 months ]
- Assessment of biomarkers in biopsy and post-operative material [ Time Frame: 60 months ]HIF-1 (hypoxia-inducible factor 1) - marker of hypoxia, predicting tumor response on radiotherapy; CD105/CD31/VEGF-A - tumor microvessel density; CD14, CD163, CD68KP i CD68 PG-M1 - tumor associated macrophages.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03651375
|Contact: Mateusz J Spałek, MDemail@example.com|
|Contact: Hanna Koseła-Paterczyk, MD PhDfirstname.lastname@example.org|
|Maria Sklodowska-Curie Institute - Oncology Center||Recruiting|
|Warsaw, Mazovian, Poland, 02-781|
|Contact: Piotr Rutkowski, MD PhD Professor +48226439375 email@example.com|
|Principal Investigator: Mateusz J Spałek, MD|
|Sub-Investigator: Hanna Koseła-Paterczyk, MD PhD|
|Sub-Investigator: Aneta Borkowska, MD|
|Sub-Investigator: Tadeusz Morysiński, MD PhD|
|Sub-Investigator: Anna Czarnecka, MD PhD|
|Sub-Investigator: Paweł Rogala, MD|
|Sub-Investigator: Monika Dudzisz-Śledź, MD PhD|
|Sub-Investigator: Tomasz Goryń, MD|
|Sub-Investigator: Maciej Sałamacha, MD|
|Sub-Investigator: Anna Szumera-Ciećkiewicz, MD PhD|
|Sub-Investigator: Michał Wągrodzki, MD|
|Sub-Investigator: Andrzej Cieszanowski, MD PhD Professor|
|Sub-Investigator: Patrycja Castaneda-Wysocka, MD|
|Sub-Investigator: Piotr Rutkowski, MD PhD Professor|