COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00652860
Recruitment Status : Completed
First Posted : April 4, 2008
Last Update Posted : May 16, 2011
National Cancer Institute (NCI)
Information provided by:
Mayo Clinic

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:



  • 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.


  • 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.


  • 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.


  • 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 2001
Actual Primary Completion Date : November 2006

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Pulmonary metastatic progression-free rate at 2 years

Secondary Outcome Measures :
  1. Survival
  2. Time to progression
  3. Toxicity as per NCI CTC Version 2.0
  4. Tumor response every 4 weeks during treatment

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


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.


  • No prior chemotherapy or radiotherapy for cancer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00652860

Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Scott Okuno, MD Mayo Clinic
Layout table for additonal information
Responsible Party: Scott Okuno, M.D., Mayo Clinic Identifier: NCT00652860    
Other Study ID Numbers: CDR0000582297
P30CA015083 ( U.S. NIH Grant/Contract )
MC0072 ( Other Identifier: Mayo Clinic Cancer Center )
1021-01 ( Other Identifier: Mayo Clinic IRB )
First Posted: April 4, 2008    Key Record Dates
Last Update Posted: May 16, 2011
Last Verified: May 2011
Keywords provided by Mayo Clinic:
lung metastases
stage III adult soft tissue sarcoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Liposomal doxorubicin
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors