RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of high-dose combination chemotherapy and peripheral stem cell transplantation in treating patients who have advanced or recurrent sarcoma.

Condition	Treatment or Intervention	Phase
Bone Cancer Soft Tissue Sarcoma	Drug: cisplatin  Drug: doxorubicin  Drug: filgrastim  Drug: ifosfamide  Drug: melphalan	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the feasibility of sequential high-dose chemotherapy with ifosfamide and doxorubicin followed by melphalan and cisplatin, each followed by autologous peripheral blood stem cell support, in patients with high-risk or advanced sarcomas. II. Determine the toxic effects of this regimen in these patients. III. Determine response rate and disease-free and overall survival in these patients treated with this regimen.

PROTOCOL OUTLINE: Beginning at least 4 weeks prior to the start of chemotherapy, patients receive filgrastim (G-CSF) subcutaneously daily until the completion of peripheral blood stem cell (PBSC) harvesting. Beginning 5 days after the start of G-CSF, PBSCs are collected over several days. Patients who do not mobilize sufficient cells undergo bone marrow harvest. Regimen A: Patients receive high-dose ifosfamide IV and doxorubicin IV continuously over 96 hours on days -8 to -4. 12.5% of PBSCs or bone marrow are reinfused on day -2 and 37.5% are reinfused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover. Regimen B: Beginning at least 4 weeks after day 1 of Regimen A, patients receive high-dose melphalan IV followed immediately by cisplatin IV on days -11 and -4. Patients receive G-CSF IV on days -10 to -6. 12.5% of PBSCs or bone marrow are reinfused on day -3 and the remaining 37.5% are reinfused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover. Patients are followed monthly for 1 year, every 3 months for 1 year, and then as needed for 3 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  10 Years   -   55 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed sarcomas in the following categories: Soft tissue sarcoma (STS); High-grade STS of the extremities; Primary extending to fascia or locally recurrent; At least 10 cm in greatest dimension or multifocal on surgical pathology; Primary site controlled by surgery and/or radiotherapy
• High-grade truncal or head and neck sarcoma; At least 10 cm in greatest dimension or any size with no surgical options for clear margins; Primary site controlled by surgery and/or radiotherapy
• Locally recurrent disease in CR or PR after surgery, chemotherapy, or radiotherapy
• Metastatic STS in CR or PR after surgery, chemotherapy, or radiotherapy
• Osteosarcoma (OS); Extremity OS after neoadjuvant chemotherapy and surgical resection provided: Less than 50% necrosis in the surgical specimen; LDH or alkaline phosphatase greater than 2 times normal at presentation; Axial OS in CR or PR after chemotherapy and/or surgery; Primary or recurrent metastatic OS in CR or PR after chemotherapy, surgery, and/or radiotherapy
• Ewing's sarcoma or primitive neuroectodermal tumor; Primary site in CR or PR after chemotherapy, radiotherapy, or surgery; Rib, pelvic, or axial skeleton primary; Bulky tumor (at least 10 cm in greatest diameter); Primary or recurrent metastatic disease in CR or PR after surgery, chemotherapy, or radiotherapy
• Rhabdomyosarcoma; Gross residual disease after primary treatment with surgery, chemotherapy, and radiotherapy; Primary group IV or recurrent metastatic disease in CR or PR after chemotherapy and radiotherapy with or without surgery
• No brain metastasis
• No histologically confirmed bone marrow metastasis; Prior metastases allowed with clearing of bone marrow at entry
• No contraindication to collection of mobilized stem cells or, if needed, autologous bone marrow

--Prior/Concurrent Therapy--

• More than 2 weeks since treatment to control primary or recurrent tumor
• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics; No more than 2 prior chemotherapy regimens (including adjuvant therapy); Prior cumulative cisplatin dose less than 400 mg/m2; Prior cumulative doxorubicin dose less than 240 mg/m2
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; No prior radiotherapy to more than 20% of the bone marrow-containing axial skeleton; No prior radiotherapy to the left chest wall
• Surgery: See Disease Characteristics

--Patient Characteristics--

• Age: 10 to 55
• Performance status: Karnofsky 80-100%
• Hematopoietic: Absolute neutrophil count greater than 2,000/mm3; Platelet count greater than 150,000/mm3; Hemoglobin greater than 10 g/dL
• Hepatic: See Disease Characteristics; Bilirubin less than 1.5 mg/dL; AST and ALT less than 3 times normal; Hepatitis B surface antigen negative; Negative hepatitis C antigen test required in patients with hepatitis C antibody
• Renal: Creatinine less than 1.4 mg/dL; Creatinine clearance greater than 75 mL/min
• Cardiovascular: LVEF at least 55% by MUGA or echocardiogram; No history of significant cardiac disease
• Pulmonary: FEV1 greater than 2 liters; PaO2 greater than 70 mm; Hg on room air; PaCO2 less than 42 mm Hg on room air; DLCO greater than 60% predicted
• Other: No hearing loss of greater than 40 decibels; HIV negative; No organic or psychiatric CNS dysfunction that would preclude study; No other medical or psychosocial problems that would place patient at unacceptable risk; No history of other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix; Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception

California
      Cancer Center and Beckman Research Institute, City of Hope, Duarte,  California,  91010-3000,  United States

Study chairs or principal investigators

George Somlo,  Study Chair,  Beckman Research Institute   

Study ID Numbers:  CDR0000063845; CHNMC-IRB-94072; NCI-V94-0545
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002601
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08