Combination Chemotherapy and Dexrazoxane Followed by Surgery and Radiation Therapy in Treating Patients With Advanced Soft Tissue Sarcoma or Recurrent Bone Sarcoma
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Purpose
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, ifosfamide, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as dexrazoxane, may protect normal cells from the side effects of chemotherapy. Giving combination chemotherapy together with dexrazoxane before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving radiation therapy 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 dexrazoxane followed by surgery and radiation therapy works in treating patients with advanced soft tissue sarcoma or recurrent bone sarcoma.
| Condition | Intervention | Phase |
|---|---|---|
|
Sarcoma |
Biological: filgrastim Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: irinotecan hydrochloride Genetic: protein expression analysis Other: immunoenzyme technique Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | Phase II Trial of Neoadjuvant Dose-Dense Doxorubicin, Ifosfamide, and Irinotecan (CPT-11) for Advanced Soft Tissue and Recurrent Bone Sarcomas |
- Response rate [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Overall survival [ Designated as safety issue: No ]
- Disease-free survival [ Designated as safety issue: No ]
| Estimated Enrollment: | 44 |
| Study Start Date: | August 2001 |
| Estimated Primary Completion Date: | October 2012 (Final data collection date for primary outcome measure) |
OBJECTIVES:
- To evaluate the effectiveness of neoadjuvant dose-dense chemotherapy comprising doxorubicin hydrochloride, ifosfamide, and irinotecan hydrochloride in combination with dexrazoxane hydrochloride followed by surgery and radiotherapy in patients with advanced soft tissue sarcoma or recurrent bone sarcoma.
- To evaluate the toxicities of this regimen in these patients.
- To compare the duration of disease-free and overall survival of patients with advanced soft tissue sarcoma who receive this therapy on a neoadjuvant basis with historical controls.
- To evaluate laboratory correlates of chemotherapy resistance for the cytotoxic agents used in this study.
OUTLINE: Patients are stratified by type of sarcoma (soft tissue vs bone), prior treatment (untreated vs treated), and presence of metastases (yes vs no).
- Courses 1 and 2: Patients receive doxorubicin hydrochloride and dexrazoxane hydrochloride IV continuously over 96 hours. Treatment repeats every 3 weeks for 2 courses.
- Courses 3 and 4: Patients receive ifosfamide IV over 2 hours twice a day (every 12 hours) on days 1-3. Treatment repeats every 3 weeks for 2 courses.
- Courses 5 and 6: Patients receive irinotecan hydrochloride IV over 1 hour once a day on days 1-5 and 8-12. Treatment repeats every 3 weeks for 2 courses.
Patients also receive filgrastim (G-CSF) subcutaneously once a day beginning 3 days after completion of chemotherapy and continuing until blood counts recover.
Patients then undergo standard surgery and radiotherapy.
Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for MDR (multidrug resistance gene) protein expression via immunoperoxidase staining.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then once a year thereafter.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Primary soft tissue sarcoma at high-risk* for recurrence, meeting any of the following criteria:
- Previously untreated locally advanced, nonmetastatic disease
- Advanced (metastatic) disease not amenable to standard or higher priority investigational neoadjuvant therapies
Recurrent bone sarcoma (e.g., osteogenic sarcoma, Ewing sarcoma, or peripheral neuroectodermal tumor)
- Must have advanced locally recurrent or metastatic disease NOTE: *High-risk is defined as high-grade, deep to fascia, and > 5 cm in greatest dimension
- Measurable or nonmeasurable disease is not required
- Pre-chemotherapy consultation with surgery and radiation oncology is required for formulation of loco-regional therapy
- No gastrointestinal stromal cell sarcoma
- No alveolar soft part sarcoma
No symptomatic brain metastases
- No requirement for anticonvulsant or corticosteroid therapy
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- Life expectancy ≥ 2 months
- Absolute neutrophil count ≥ 2,000/mm^3
- Platelet count > 120,000/mm^3
- Creatinine clearance > 50 mL/min
- Serum bilirubin ≤ 1.5 mg/dL
- SGOT or SGPT ≤ 2.5 times upper limit of normal
- Serum albumin ≥ 2.5 mg/dL
- LVEF ≥ 50% by MUGA scan
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No concurrent nonmalignant illness (e.g., cardiovascular, pulmonary, or CNS disease) that is poorly controlled with currently available treatment or is of such severity that the investigators deem it unwise for the patient to enter the study
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy for recurrent (local or metastatic) soft tissue sarcoma
- Prior chemotherapy for recurrent bone sarcoma allowed provided the total dose of doxorubicin hydrochloride is ≤ 300 mg/m^2
- No prior radiotherapy to > 25% of bone marrow
- At least 3 weeks since prior radiotherapy or chemotherapy
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT00544778 History of Changes |
| Other Study ID Numbers: | 00050, P30CA033572, CHNMC-00050, CDR0000566381 |
| Study First Received: | October 13, 2007 |
| Last Updated: | October 17, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by City of Hope Medical Center:
|
recurrent adult soft tissue sarcoma stage III adult soft tissue sarcoma stage IV adult soft tissue sarcoma metastatic osteosarcoma |
recurrent osteosarcoma metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor Ewing sarcoma of bone |
Additional relevant MeSH terms:
|
Osteosarcoma Neuroectodermal Tumors, Primitive, Peripheral Sarcoma Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Doxorubicin |
Isophosphamide mustard Irinotecan Ifosfamide Razoxane Camptothecin Lenograstim Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Cardiovascular Agents Chelating Agents |
ClinicalTrials.gov processed this record on October 17, 2012
