Neoplasms

Symptoms and General Pathology

All Conditions

Rare Diseases

Neoplasm Metastasis

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Molgramostim

Sargramostim

Cisplatin

Ifosfamide

Mitomycins

Mitomycin

Isophosphamide mustard

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunologic Factors

aerosol sargramostim

sargramostim

cisplatin

doxorubicin hydrochloride

ifosfamide

mitomycin C

flow cytometry

immunological diagnostic method

laboratory biomarker analysis

adjuvant therapy

multimodality therapy

neoadjuvant therapy

therapeutic conventional surgery

intraoperative radiation therapy

selective external radiation therapy

Scott Okuno, MD

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.

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.

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

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

National Cancer Institute (NCI)

Mayo Clinic

Scott Okuno, M.D.

Nervous System Diseases

Histiocytoma, Malignant Fibrous

Liposarcoma

Fibrosarcoma

Histiocytoma

Histiocytoma, Benign Fibrous

Hemangiosarcoma

Leiomyosarcoma

Rhabdomyosarcoma

Sarcoma, Synovial

Neurofibrosarcoma

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Epithelioid Sarcoma

pegfilgrastim

Ian R. Judson, MA, MD, FRCP

RATIONALE: Drugs used in chemotherapy such as doxorubicin and ifosfamide use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors, such as pegfilgrastim, cause the body to make blood cells. It is not yet known whether doxorubicin alone is more effective with or without ifosfamide and pegfilgrastim in treating soft tissue sarcoma.

PURPOSE: This randomized phase III trial is studying giving doxorubicin alone to see how well it works compared to giving doxorubicin together with ifosfamide and pegfilgrastim in treating patients with locally advanced or metastatic soft tissue sarcoma.

OBJECTIVES:

* Compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin with vs without ifosfamide and pegfilgrastim as first-line therapy.
* Compare the response in patients treated with these regimens.
* Compare the treatment-related mortality of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to WHO performance status (0 vs 1), age group (less than 50 years of age vs 50 years of age and over), presence of liver metastases (yes vs no), histological grade (2 vs 3), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive doxorubicin IV on day 1 (or IV continuously on days 1-3).
* Arm II: Patients receive doxorubicin IV on days 1-3 and ifosfamide IV over 4 hours on days 1-4. Patients also receive pegfilgrastim subcutaneously on day 5.

In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 4 years.

Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma

Randomised Trial Of Single Agent Doxorubicin Versus Doxorubicin Plus Ifosfamide In The First Line Treatment Of Advanced Or Metastatic Soft Tissue Sarcoma

European Organisation for Research and Treatment of Cancer - EORTC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Combination Chemotherapy, Radiation Therapy, and Sargramostim Before and After Surgery in Treating Patients With Soft Tissue Sarcoma That Can Be Removed By Surgery	NCT00652860	Metastatic Canc... Sarcoma	aerosol sargram... sargramostim cisplatin doxorubicin hyd... ifosfamide mitomycin C flow cytometry immunological d... laboratory biom... adjuvant therap... multimodality t... neoadjuvant the... therapeutic con... intraoperative ... selective exter...	18 Years -	Mayo Clinic
Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma	NCT00061984	Sarcoma	pegfilgrastim doxorubicin hyd... ifosfamide multimodality t...	18 Years - 60 Years	European Organisation for Research and Treatment of Cancer - EORTC

Spots Global Cancer Trial Database for multimodality therapy