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

Sponsors and Collaborators:	Mayo Clinic National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00652860

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	Drug: aerosol sargramostim Drug: cisplatin Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mitomycin C Drug: sargramostim Procedure: adjuvant therapy Procedure: flow cytometry Procedure: immunological diagnostic method Procedure: intraoperative radiation therapy Procedure: laboratory biomarker analysis Procedure: multimodality therapy Procedure: neoadjuvant therapy Procedure: selective external radiation therapy Procedure: therapeutic conventional surgery	Phase II

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Ifosfamide Cisplatin Sargramostim Granulocyte-macrophage colony-stimulating factor Mitomycin Mitomycins

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

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
Estimated Primary Completion Date:	December 2010 (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

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

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Scott Okuno, MD

Mayo Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000582297, MAYO-MC0072
Study First Received:	April 3, 2008
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00652860
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

lung metastases
stage III adult soft tissue sarcoma

Study placed in the following topic categories:

Neoplasms, Connective and Soft Tissue
Ifosfamide
Cisplatin
Malignant mesenchymal tumor
Mitomycin
Neoplasm Metastasis

Sarcoma
Mitomycins
Doxorubicin
Soft tissue sarcomas
Isophosphamide mustard

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Antibiotics, Antineoplastic
Pharmacologic Actions
Neoplastic Processes

Neoplasms
Pathologic Processes
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009