Neoadjuvant and Adjuvant Chemotherapy in High-risk Soft Tissue Sarcoma

Phase 2

Completed

• Conditions: Soft Tissue Sarcoma
• Interventions: Drug: EIA chemotherapy

• Registration Number: NCT01382030
• Lead Sponsor: Heidelberg University

Brief Summary

Neo- and adjuvant chemotherapy is used in high-risk soft tissue sarcoma to improve systemic control. Patients in this trial are treated with 4 cycles of chemotherapy (EIA, etoposide, ifosfamide, adriamycin) preoperatively, followed by local surgery and radiotherapy. An additional 4 cycles of adjuvant chemotherapy is administered. Treatment response is assessed by MRI and CT scans and FDG-PET in a subgroup of patients.

Detailed Description

The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event resulting in 5-year overall survival rates of only 50 - 60%. Neo-adjuvant and adjuvant chemotherapy has been applied to achieve pre-operative cytoreduction, assess chemosensitivity and to eliminate occult metastasis. The current protocol comprises for cycles of neoadjuvant chemotherapy ((EIA, etoposide 125 mg/m2 iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m2 day 1, pegfilgrastim 6 mg sc day 5), local surgery and radiotherapy as well as further 4 cycles of adjuvant EIA. Treatment response is assessed by MRI and CT scans and FDG-PET in a subgroup of patients.

Study Timeline

• Study Start: 2005-06
• Primary Completion: 2010-09
• Study Completion: 2011-01
• Status Verified: 2011-06
• Study First Submitted: 2011-06-17
• Study First Submitted QC: 2011-06-23
• Last Update Submitted: 2011-06-23
• Study First Posted: 2011-06-27
• Last Update Posted: 2011-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Soft tissue sarcoma histology
• Tumor size >= 5 cm
• Deep/extracompartimental localization
• Grade 2/3 (FNCLCC)
• Patients with inadequate previous therapy
• Age 18-65 years
• normal bone marrow function
• normal liver function
• normal renal function
• Karnofsky index >=80%

Exclusion Criteria

• Chordoma
• Chondrosarcoma
• Kaposi´ sarcoma
• Neuroblastoma
• Mesothelioma
• Osteosarcoma/Ewings´sarcoma

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	EIA chemotherapy	All patients receive 4 cycles of EIA chemotherapy pre- and postoperatively. There is no further observation arm. The study is non-randomized.

Primary Outcome Measures

Name	Time	Method
Disease-free survival	2 years after study completion	Disease-free survival will be calculated from the time of definite surgery to radiologically proven local or distant failure or patient´s death due to sarcoma related cause.

Secondary Outcome Measures

Name	Time	Method
Radiologic Tumor Response	Every 6 weeks for an average of 8 months, then every 3 months for 2 years	Tumor response to therapy will be assessed by MRI and CT scans. Response will graded according to RECIST criteria.
Cardiac Toxicity	Every 6 weeks for an average of 8 months	Changes in cardiac ejection fraction will be assessed by echocardiograms. Toxicities will be graded according to CTCAE.
Overall Survival	2 years after study completion	Overall survival will be calculated as the time interval from the date of therapy induction to patient's death or last follow up.
Grade of histological necrosis	After definite surgery, approx. 12-15 weeks after study inclusion	Grade of histological necrosis in tumor specimen will be assessed after surgery and graded according to Salzer-Kuntschik.
Hematological toxicity	Once weekly for an average of 8 months	Hematological toxicity will be assessed by complete blood counts. Toxicity will be graded according to CTCAE.
Renal Toxicity	Once weekly for an average of 8 months	Renal toxicity will be assessed by changes from baseline creatinin levels. Toxicity will be graded according to CTCAE.
Liver Toxicity	Once weekly for an average of 8 months	Liver toxicity will be assessed by changes from baseline liver function tests, e.g. ASAT/ALAT. Toxicity will be graded according to CTCAE.
Correlation of Tumor Necrosis and Decline in PET SUV	After tumor resection, approx. 12-15 weeks after study inclusion	Decline in PET SUV will be correlated with grade of histological necrosis in tumor specimen after surgery.

Trial Locations

Locations (1)

Heidelberg University Clinics; 🇩🇪 Heidelberg, Baden-Wuerttemberg, Germany