Combination Chemotherapy Before and After Surgery in Treating Patients With Osteosarcoma

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00019864

Collaborator

(none)

100

Enrollment

Locations

139

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Toxicity Sarcoma	Biological: filgrastim Drug: cisplatin Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: leucovorin calcium Drug: methotrexate Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Study Start Date :

Mar 1, 2000

Actual Primary Completion Date :

Dec 1, 2006

Actual Study Completion Date :

Oct 1, 2011

Outcome Measures

Primary Outcome Measures

Rate of in vivo histologic response []
Event-free survival []
Overall survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892-1182
2	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
3	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
4	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Houston	Texas	United States	77030-2399