Neoadjuvant and Adjuvant Chemotherapy in High-risk Soft Tissue Sarcoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Study Evaluating Neo-/Adjuvant EIA Chemotherapy, Surgical Resection and Radiotherapy in High-risk Soft Tissue Sarcoma

Conditions
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Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: EIA chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>All patients receive 4 cycles of EIA chemotherapy pre- and postoperatively. There is no further observation arm. The study is non-randomized. | Drug: EIA chemotherapy<br>* ifosfamide 1500 mg/m² iv days 1 - 4, etoposide 125 mg/m² iv days 1 and 4, and adriamycin 50 mg/m² iv day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | 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. | 2 years after study completion | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Soft tissue sarcoma, High-risk, Neoadjuvant, Adjuvant, Chemotherapy, Radiotherapy