Combination Chemotherapy, Radiation Therapy, and Sargramostim Before and After Surgery in Treating Patients With Soft Tissue Sarcoma That Can Be Removed By Surgery

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00652860

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. GM-CSF may stimulate the immune system in different ways and stop tumor cells from growing. GM-CSF, given by inhalation, may interfere with the growth of tumor cells and prevent metastases from forming. Radiation therapy uses high energy x rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy and GM-CSF before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy and GM-CSF before and after surgery works in treating patients with stage III soft tissue sarcoma that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Cancer Sarcoma	Biological: aerosol sargramostim Biological: sargramostim Drug: cisplatin Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mitomycin C Other: flow cytometry Other: immunological diagnostic method Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: multimodality therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Radiation: intraoperative radiation therapy Radiation: selective external radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Primary

To evaluate 2-year pulmonary metastatic progression rates in patients with primary high-grade extremity soft tissue sarcoma who have received preoperative I-MAP, plus aerosol GM-CSF, plus irradiation with concomitant MAP followed by post-operative aerosol GM-CSF.

Secondary

To evaluate survival of these patients.
To evaluate time to progression in these patients.
To evaluate toxicity in these patients.
To evaluate tumor response in these patients.

Translational

To observe and describe sequentially before treatment, after treatment, and after recovery from treatment the frequency of skin test anergy and cellular immunity in extremity soft tissue sarcoma receiving systemic GM-CSF preoperatively and aerosol GM-CSF as part of both preoperative and postoperative treatment.

OUTLINE:

Neoadjuvant treatment: Patients receive ifosfamide IV over 2 hours on days 0 and 1 and cisplatin IV over 4 hours, mitomycin IV and doxorubicin IV on day 1. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) every 12 hours on days -6 to -3, 2-14, and 22-25. Beginning on day 84 patients also undergo radiotherapy once daily, five days a week, continuing for five weeks. Patients also receive GM-CSF SC twice daily on days -3 and 2 -15 and aerosol GM-CSF twice daily on days 85 - 91, 99 -105, and 113 - 119.
Chemoradiotherapy: Beginning 4 weeks after completion of neoadjuvant chemotherapy, patients undergo radiotherapy (RT) once daily, 5 days a week, for 5 weeks. Patients also receive aerosolized GM-CSF twice daily on days 2-8, 16-22, and 30-38 and mitomycin C IV, doxorubicin hydrochloride IV, and cisplatin IV over 2 hours on days 1 and 29.
Surgery: Four weeks after completion of chemotherapy, patients undergo surgery. Patients may also undergo intraoperative RT electron boost or intraoperative high-dose brachytherapy.
Adjuvant treatment: Beginning 4 weeks after surgery, patients receive aerosol GM-CSF twice daily on days -7, 15-21, 35-42, 56-63, and 77-84. Some patients may undergo external beam RT 2-4 weeks after surgery.

Blood samples are collected at baseline and at 4 and 14 weeks after surgery. Samples are tested for NY-ESO-1 by staining, for T-cell subset by flow cytometry, and for autologous lymphocyte proliferation. Patients may also be tested for delayed-type hypersensitivity and skin test anergy.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and at 5 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

39 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Chemotherapy, Irradiation, and Surgery for Function-Preserving Curative Therapy of Primary Extremity Soft Tissue Sarcomas: Initial Treatment With I-MAP and GM-CSF; Aerosol GM-CSF During Preoperative Irradiation and Postoperatively

Study Start Date :

Aug 1, 2001

Actual Primary Completion Date :

Nov 1, 2006

Outcome Measures

Primary Outcome Measures

Pulmonary metastatic progression-free rate at 2 years []

Secondary Outcome Measures

Survival []
Time to progression []
Toxicity as per NCI CTC Version 2.0 []
Tumor response every 4 weeks during treatment []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed primary soft tissue sarcoma
Sarcoma must be of the extremity or limb girdle origin
No metastatic disease
High-grade
Must be a candidate for preoperative irradiation for potential limb-sparing surgery
Must not have any of the following:
Embryonal rhabdomyosarcoma
Extraosseous Ewing sarcomas