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Combination Chemotherapy Before and After Surgery in Treating Patients With Osteosarcoma

This study is ongoing, but not recruiting participants.
Study NCT00019864.   Last updated on October 18, 2008.   Information provided by National Cancer Institute (NCI)

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Descriptive Information Fields
Brief Title  Combination Chemotherapy Before and After Surgery in Treating Patients With Osteosarcoma
Official Title  Osteosarcoma: Outcome of Therapy Based on Histologic Response. A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma.
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed during surgery. Giving chemotherapy after surgery may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving chemotherapy before and after surgery works in treating patients with osteosarcoma.

Detailed Description

OBJECTIVES:

  • Determine the rate of in vivo histologic response in patients with osteosarcoma treated with neoadjuvant cisplatin, methotrexate, and doxorubicin with dexrazoxane (as cardioprotection).
  • Determine the event-free and overall survival of patients with nonmetastatic disease who show good response to neoadjuvant therapy and receive adjuvant therapy with the same regimen.
  • Determine the event-free survival of patients with nonmetastatic disease who show poor response to neoadjuvant therapy and receive adjuvant therapy with the same regimen.
  • Determine the event-free survival and overall survival of patients with metastatic disease who receive neoadjuvant therapy.

OUTLINE: This is a multicenter study.

  • Neoadjuvant therapy: Patients receive neoadjuvant chemotherapy comprising dexrazoxane IV over 15 minutes, doxorubicin IV over 15 minutes, and cisplatin IV over 4 hours on days 1 and 2 in week 0. Patients also receive methotrexate IV over 4 hours followed by leucovorin calcium in weeks 3 and 4. Patients then receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Treatment repeats every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
  • Surgical resection: Patients undergo definitive surgery in week 11.
  • Adjuvant therapy: Patients receive dexrazoxane, doxorubicin, cisplatin, methotrexate, and leucovorin calcium as in neoadjuvant therapy*. Treatment repeats every 5 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Cisplatin is not administered in courses 3 and 4 of adjuvant therapy

Patients are followed within 4 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.

Study Phase Phase II
Study Type  Interventional
Study Design  Treatment, Open Label
Primary Outcome Measure  Rate of in vivo histologic response [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Secondary Outcome Measure 
Condition  Cancer-Related Problem/Condition
Sarcoma
Intervention  Drug: cisplatin
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: filgrastim
Drug: leucovorin calcium
Drug: methotrexate
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
MEDLINE PMIDs
Links Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Active, not recruiting
Enrollment  100
Start Date  March 2000
Completion Date
Eligibility Criteria 

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed osteosarcoma

    • No more than 1 month since prior diagnostic biopsy
    • Nonmetastatic malignant high-grade osteosarcoma of bone
    • Histologically confirmed metastatic disease allowed
    • Unresectable primary disease allowed
  • No low-grade, parosteal, or periosteal osteosarcoma

PATIENT CHARACTERISTICS:

Age:

  • 25 and under

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 8.0 g/dL

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • ALT less than 5 times normal

Renal:

  • Creatinine no greater than 1.5 times normal
  • Creatinine clearance or radioisotope glomerular filtration rate greater than 70 mL/min

Cardiovascular:

  • Shortening fraction at least 27% by echocardiogram or MUGA
  • Ejection fraction at least 45% by echocardiogram or MUGA

Other:

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics
  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics

Surgery:

  • Not specified

Other:

  • No other concurrent therapy with no evidence of progressive disease
Gender Both
Ages up to 25 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United States
Administrative Information Fields
NCT ID  NCT00019864
Organization ID CDR0000067263
Secondary IDs †† NCI-99-C-0125I
Study Sponsor  NCI - Center for Cancer Research-Medical Oncology
Collaborators †† National Cancer Institute (NCI)
Investigators 
Study Chair:     Ramzi Dagher, MD     NCI - Pediatric Oncology Branch    
Information Provided By National Cancer Institute (NCI)
Verification Date October 2007
First Received Date  July 11, 2001
Last Updated Date October 18, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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