Ifosfamide, Doxorubicin and Hypofractionated Radiotherapy in Neoadjuvant Sarcoma Treatment

Study Overview
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Brief Summary
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Prospective phase II study. Patients will be submitted to neoadjuvant chemotherapy (cT) and hypo fractionated radiotherapy (hRT) following by surgery. The remain viable cells will be analyzed and the patients whithin less than 30% will receive more 3 cycles of cT. All patients have deep high grade soft tissue sarcoma of extremity.

Detailed Description
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Prospective phase II non controlled study. Staging: All patients will be submitted to a local Magnetic Resonance (MR), Chest Tomography (CT) and Positron emission tomography-computed tomography (PET CT) previous to treatment. After the first cT cycle a new PET CT will be provided and one more at the end of the neoadjuvant treatment. Chemotherapy: cT neoadjuvant: Doxorubicin 75mg/m2 (cycles 1,2 and 3), and ifosfamide 9 g/m2 (cycles 1 and 3). Radiotherapy: RT 25 Gy / 5 x 500 cGy/day, beginning at Cycle 2/Day1. The surgery will be performed after 4-6 weeks from cycle 3. The remain of viable cells in surgical specimen will be analyzed and whether the the percentage value is less than 30% the patient will receive more 3 cycles of cT. A boost of RT is indicated if margins are considered R1 (microscopic positive margin).

Official Title
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The Use of Ifosfamide, Doxorubicin and Hypofractionated Radiotherapy in Neoadjuvant Treatment of High-grade Extremity Soft Tissue and Non-metastatic Sarcomas

Conditions
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Sarcoma, Soft Tissue

Intervention / Treatment
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* Drug: Doxorubicin
* Drug: Ifosfamide
* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18-75 years old, with non metastatic deeply high grade soft tissue sarcoma of extremities. KPS > 70% (Karnofsky Performance Status Score) Exclusion Criteria: Patients with rhabdomyosarcoma, neuroendocrine tumor (Pnet) and chondrosarcomas, or who have had received radiotherapy (RT) or chemotherapy (cT) previous, or recurrent tumors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxorubicin, Ifosfamide, radiotherapy<br>Doxorubicin 75mg/m2 (cycle 1,2 and 3), ifosfamide 9 g/m2 (cycle 1 and 3) and radiotherapy: 25 Gy / 5 x 500 cGy/day, beginning at Cycle2/Day1. The surgery will performed after 4-6 weeks from cycle 3. The remain viable cells in surgical specimen will be analyzed and if it accounts less than 30% the patient will receive more 3 cycles of cT. A boost of RT is indicated if margins are considered R1. | Drug: Doxorubicin<br>* Doxorubicin 75mg/m2 (cycle 1,2 and 3)<br>* Other names: Adriamycin;Drug: Ifosfamide<br>* Ifosfamide 9 g/m2 (cycle 1 and 3)<br>* Other names: Mitoxana;Radiation: radiotherapy<br>* radiotherapy: 25 Gy / 5 x 500 cGy/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate disease free survival after neoadjuvant treatment | Evaluate local and distant disease free survival after the treatment | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate wound complication rates | Evaluate if this treatment is comparable with the Institution previous results using only cT as neoadjuvant treatment (20% of wound complications). | 30 days | 
| Amputation rates | Evaluate if it can be maintained the amputation rate (less than 5%) | 30 days | 
| cT morbidity | Evaluate the morbidity rates related to cT scheme | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcoma, soft tissue sarcoma, neoadjuvant chemotherapy, neoadjuvant radiotherapy, hypofractionated radiotherapy