Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Sarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00002601
First received: November 1, 1999
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Sarcoma
Biological: filgrastim
Drug: cisplatin
Drug: doxorubicin hydrochloride
Drug: ifosfamide
Drug: melphalan
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High-Dose Doxorubicin and Ifosfamide Followed by Melphalan and Cisplatin for Patients With High-Risk and Recurrent Sarcoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Evaluate the feasibility of administration of two cycles of high-dose chemotherapy followed by autologous stem cell support in patients with high-risk or advanced sarcomas. [ Time Frame: 2 years after completion of treatment ] [ Designated as safety issue: No ]
  • Evaluate the toxicities of two cycles of sequential high-dose chemotherapy with autologous stem cell support. [ Time Frame: 2 months after completion of second cycle of treatment. ] [ Designated as safety issue: Yes ]
  • Evaluate the effectiveness of sequential high-dose chemotherapy followed by autologous stem cell support in patients with high-risk or advanced sarcoma for response, disease-free survival and overall survival. [ Time Frame: Two years after completion of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 1994
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: filgrastim
    5 ug/kg daily following stem cell reinfusion
    Drug: cisplatin
    Course 2 - 100 mg/m2 at an infusion rate of 25 mg/hr
    Drug: doxorubicin hydrochloride
    Course 1 - 150 mg/m2 by continuous intravenous infusion for 96 hours.
    Drug: ifosfamide
    Course 1 - 14 gm/M2 by continuous intravenous infusion for 96 hours.
    Drug: melphalan
    Course 2 - 75 mg/m2 infused at a rate of 5 mg/minute
    Procedure: peripheral blood stem cell transplantation
    Administered on Day 0 following high-dose chemotherapy in both courses 1 and 2
Detailed Description:

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.

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.

  Eligibility

Ages Eligible for Study:   10 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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

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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00002601

Locations
United States, California
Cancer Center and Beckman Research Institute, City of Hope
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: George Somlo, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00002601     History of Changes
Other Study ID Numbers: 94072, P30CA033572, CHNMC-IRB-94072, NCI-V94-0545, CDR0000063845
Study First Received: November 1, 1999
Last Updated: May 13, 2014
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
metastatic osteosarcoma
recurrent childhood rhabdomyosarcoma
recurrent adult soft tissue sarcoma
recurrent osteosarcoma
adult rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
previously treated childhood rhabdomyosarcoma
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
stage IV adult soft tissue sarcoma

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Connective and Soft Tissue
Isophosphamide mustard
Cisplatin
Doxorubicin
Ifosfamide
Melphalan
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 22, 2014