Ifosfamide, Doxorubicin and Hypofractionated Radiotherapy in Neoadjuvant Sarcoma Treatment

Sarcoma, Soft Tissue Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02812654
• Other study ID #: 1947/14
• Status: Recruiting
• Phase: Phase 2
• First received: March 24, 2016
• Last updated: June 22, 2016
• Start date: March 2015
• Est. completion date: March 2019

Study information

• Verified date: March 2016
• Source: AC Camargo Cancer Center
• Contact: Ademar Lopes, Phd
• Phone: 55-11-2189-5000
• Email: ademar-lopes[@]uol.com.br
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Soft Tissue

Intervention

Drug:
• Doxorubicin
Doxorubicin 75mg/m2 (cycle 1,2 and 3)
• Ifosfamide
Ifosfamide 9 g/m2 (cycle 1 and 3)

Radiation:
• radiotherapy
radiotherapy: 25 Gy / 5 x 500 cGy/day

Locations

Country	Name	City	State
Brazil	A.C.Camargo Cancer Center	São Paulo	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
AC Camargo Cancer Center

Country where clinical trial is conducted

Brazil, 

References & Publications (8)

Aguiar Junior S, Ferreira Fde O, Rossi BM, Santos EM, Salvajoli JV, Lopes A. Neoadjuvant chemoradiation therapy for soft tissue sarcomas of the extremities. Clinics (Sao Paulo). 2009;64(11):1059-64. doi: 10.1590/S1807-59322009001100005. — View Citation

Aguiar S Jr, da Cunha IW, Lopes A. Genomic expression, chemotherapy response, and molecular targets in soft tissue sarcomas of the extremities: promising strategies for treatment selection. J Surg Oncol. 2010 Jan 1;101(1):92-6. doi: 10.1002/jso.21422. Review. — View Citation

Benz MR, Czernin J, Allen-Auerbach MS, Tap WD, Dry SM, Elashoff D, Chow K, Evilevitch V, Eckardt JJ, Phelps ME, Weber WA, Eilber FC. FDG-PET/CT imaging predicts histopathologic treatment responses after the initial cycle of neoadjuvant chemotherapy in high-grade soft-tissue sarcomas. Clin Cancer Res. 2009 Apr 15;15(8):2856-63. doi: 10.1158/1078-0432.CCR-08-2537. Epub 2009 Apr 7. — View Citation

Cormier JN, Huang X, Xing Y, Thall PF, Wang X, Benjamin RS, Pollock RE, Antonescu CR, Maki RG, Brennan MF, Pisters PW. Cohort analysis of patients with localized, high-risk, extremity soft tissue sarcoma treated at two cancer centers: chemotherapy-associated outcomes. J Clin Oncol. 2004 Nov 15;22(22):4567-74. — View Citation

Eilber FC, Rosen G, Nelson SD, Selch M, Dorey F, Eckardt J, Eilber FR. High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality. Ann Surg. 2003 Feb;237(2):218-26. — View Citation

Freedman GM. Hypofractionated radiation therapy in the treatment of early-stage breast cancer. Curr Oncol Rep. 2012 Feb;14(1):12-9. doi: 10.1007/s11912-011-0207-7. Review. — View Citation

Grobmyer SR, Maki RG, Demetri GD, Mazumdar M, Riedel E, Brennan MF, Singer S. Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol. 2004 Nov;15(11):1667-72. — View Citation

Gronchi A, Frustaci S, Mercuri M, Martin J, Lopez-Pousa A, Verderio P, Mariani L, Valagussa P, Miceli R, Stacchiotti S, Dei Tos AP, De Paoli A, Longhi A, Poveda A, Quagliuolo V, Comandone A, Casali PG, Picci P. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012 Mar 10;30(8):850-6. doi: 10.1200/JCO.2011.37.7218. Epub 2012 Feb 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PET CT response	Evaluate if the SUV (Standard uptake value) varies after first and third cycle and if it is related to survival	3 months	No
Primary	Evaluate disease free survival after neoadjuvant treatment	Evaluate local and distant disease free survival after the treatment	24 months	No
Secondary	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	Yes
Secondary	Amputation rates	Evaluate if it can be maintained the amputation rate (less than 5%)	30 days	Yes
Secondary	cT morbidity	Evaluate the morbidity rates related to cT scheme	6 months	Yes