Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI	MAYO-MC0072 MC0072, NCT00652860

Objectives

Primary

1. 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

1. To evaluate survival of these patients.
2. To evaluate time to progression in these patients.
3. To evaluate toxicity in these patients.
4. To evaluate tumor response in these patients.

Translational

1. 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.

Entry Criteria

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

Prior/Concurrent Therapy:

• No prior chemotherapy or radiotherapy for cancer

Patient Characteristics:

Inclusion criteria:

• ECOG performance status 0 – 2
• WBC ≥ 3,500/μL OR granulocyte count ≥1,500/μL
• Platelets ≥150,000/μL
• Direct-reacting bilirubin ≤ 0.3 mg/dL
• Creatinine ≤1.2 times the upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria:

• Significant infection
• Active heart disease including any of the following:
  • Myocardial infarction in the past 3 months
  • Symptomatic coronary artery insufficiency
  • First-degree heart block
  • Clinical history of congestive heart failure
• Symptomatic pulmonary disease.

Expected Enrollment

Outcomes

Pulmonary metastatic progression-free rate at 2 years

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

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Scott Okuno, MD, Principal investigator		Ph: 507-538-7623 Email: okuno.scott@mayo.edu

Registry Information
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
Trial Start Date		2001-08-31
Trial Completion Date		2010-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00652860
Date Submitted to PDQ		2007-12-14
Information Last Verified		2008-04-02
NCI Grant/Contract Number		CA15083