Neoadyuvant High-dose of Ifosfamide and Concurrent Radiotherapy in Soft Tissue Sarcoma

Phase II Study of Neoadyuvant High-dose Ifosfamide and Concurrent Radiotherapy in Soft Tissue Sarcoma and Identification of Response Predictors

To study the activity and toxicity of a neoadjuvant regimen including high-dose ifosfamide in combination with radiotherapy, and subsequent surgery, in high-risk soft tissue sarcomas.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Ifosfamide

Detailed Description

This is a phase II multicenter study designed in two phases. A total of 32 patients will be included in 10 hospitals belonging to the Spanish Group for Research in Sarcomas (GEIS). Selection criteria are: patients with localized soft tissue sarcoma from the extremities or trunk with high-risk features (>5 cm and grade 2-3), or recurrences after prior inadequate surgery. The treatment schedule will be: initial biopsy, 3 cycles of high-dose Ifosfamide, 12 gr/m2 in 5 days, concurrent with Radiotherapy 50 Gy, and subsequent wide surgery. To assess the predictive factors of response to the combination therapy, DNA and RNA extraction will be performed on the pretreatment biopsies. DNA will be used to hybridize Affymetrix GeneChip® Human Mapping 500K Array, which allows for the study of 500000 SNPs throughout the genome. The expression of 39000 RNA transcripts will be evaluated employing the Affymetrix Genechip Human Genome HG-U133 Plus 2.0, and validated by real-time RT-PCR.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • España
    • Barcelona, España, Spain, 08006
      • Grupo Espanol de Investigacion en Sarcomas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with Advanced Soft Tissue Sarcoma histological proven, potentially resected, located in extremities and trunk for one of the following histological subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma, Synovial Sarcoma, Liposarcoma and malignant tumour of peripheral nerve sheath.

2. Primary tumour:

   1. Size ³ 5 cm of diameter
   2. Histological grade 2-3
   3. Deep location
3. No distant metastases
4. Patients must have not been previously treated with Chemotherapy or Radiotherapy on the tumour area.
5. However patients are eligible with local relapse after previous surgery.
6. Patients must be £18 and ³ 65 years old.
7. Patients must have ECOG performance status 0 to 1
8. Patients must have measurable disease by Recist Criteria.
9. Absolute neutrophil count ³1,500/mm3, platelet count ³ 100,060 ml/min, creatinine, total bilirubin, ALT and AST £ 1.5 times the upper limit of normal
10. Signed informed consent prior to any study specific procedures

Exclusion Criteria:

1. Patients with cerebral metastasis
2. Pregnant or breast feeding patients.
3. Active infection or other concomitant severe illness.
4. Severe psychiatric illness which would not make possible the obtention of the informed consent
5. Concurrent treatment with other experimental drugs within 30 days prior to study entry.
6. History of previous treated or diagnosed cancer in the past 5 years, excepting basocellular cell skin cancer, cervix cancer in situ or superficial bladder carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Ifosfamide; 3 cycles of Ifosfamide (12g/m2) associated to Mesna (6g/m2), in i.v infusion 6 days, every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The efficacy of the neoadyuvant high-dose of ifosfamide and radiotherapy, determined with clinical and pathological responses	10 weeks since the inclusion of the patient

Secondary Outcome Measures

Outcome Measure	Time Frame
Global survival, free relapse survival and toxicity	Until relapse or patient´s death

Collaborators and Investigators

• Sponsor: Grupo Espanol de Investigacion en Sarcomas
• Investigators: Study Chair: Xavier García del Muro, Doctor, Grupo Espanol de Investigacion en Sarcomas

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: April 12, 2010
• First Submitted That Met QC Criteria: April 12, 2010
• First Posted (Estimate): April 13, 2010

Study Record Updates

• Last Update Posted (Estimate): March 20, 2012
• Last Update Submitted That Met QC Criteria: March 19, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: sarcoma; ifosfamide
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Ifosfamide
• Other Study ID Numbers: GEIS15; Nº EudraCT:2007-005755-42