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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00652860
First received: April 3, 2008
Last updated: May 13, 2011
Last verified: May 2011
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Pulmonary metastatic progression-free rate at 2 years [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Toxicity as per NCI CTC Version 2.0 [ Designated as safety issue: Yes ]
  • Tumor response every 4 weeks during treatment [ Designated as safety issue: No ]

Estimated Enrollment: 39
Study Start Date: August 2001
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00652860

Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Scott Okuno, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Scott Okuno, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00652860     History of Changes
Other Study ID Numbers: CDR0000582297, P30CA015083, MC0072, 1021-01
Study First Received: April 3, 2008
Last Updated: May 13, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
lung metastases
stage III adult soft tissue sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasm Metastasis
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Processes
Pathologic Processes
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014