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

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00652860
• Other study ID #: CDR0000582297
• Secondary ID: P30CA015083MC007
• Status: Completed
• Phase: Phase 2
• First received: April 3, 2008
• Last updated: May 13, 2011
• Start date: August 2001

Study information

• Verified date: May 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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.

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for cancer

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Sarcoma

Intervention

Biological:
• aerosol sargramostim

• sargramostim

Drug:
• cisplatin

• doxorubicin hydrochloride

• ifosfamide

• mitomycin C

Other:
• flow cytometry

• immunological diagnostic method

• laboratory biomarker analysis

Procedure:
• adjuvant therapy

• multimodality therapy

• neoadjuvant therapy

• therapeutic conventional surgery

Radiation:
• intraoperative radiation therapy

• selective external radiation therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary metastatic progression-free rate at 2 years			No
Secondary	Survival			No
Secondary	Time to progression			No
Secondary	Toxicity as per NCI CTC Version 2.0			Yes
Secondary	Tumor response every 4 weeks during treatment			No