Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Plus Dexrazoxane in Treating Patients With Newly Diagnosed Nonmetastatic Osteosarcoma

Basic Trial Information

Objectives

I. Compare the efficacy of three intensification regimens (doxorubicin vs 
doxorubicin plus ifosfamide vs doxorubicin plus ifosfamide and etoposide) in 
patients with newly diagnosed, previously untreated, nonmetastatic 
osteosarcoma.

II. Determine the effect of postoperative dose intensification on outcome in 
patients with standard response to preoperative chemotherapy.

III. Determine the effect of dexrazoxane cardioprotection during standard 
induction therapy on histologic response in these patients.

IV. Evaluate biological factors that may predict outcome in these patients.

V. Determine the safety of dexrazoxane administered with doxorubicin in 
combination with cisplatin or cisplatin and ifosfamide in these patients.

VI. Determine the effect of dexrazoxane on cytotoxicity as measured by tumor 
necrosis at definitive surgery in these patients.

VII. Assess the feasibility of administering doxorubicin with dexrazoxane 
cardioprotection or high dose ifosfamide with etoposide to standard risk 
patients who are also receiving methotrexate and cisplatin.

Entry Criteria

Disease Characteristics:

Histologically proven newly diagnosed moderate or high grade osteosarcoma
without metastases
 No prior treatment, including complete resection
 No parosteal or periosteal sarcoma
 No osteosarcoma associated with Paget's disease

No nonresectable tumors or tumors that may result in marginal or interlesion
resection

Must be enrolled on protocol POG-9851

Prior/Concurrent Therapy:

See Disease Characteristics

Biologic therapy:
 Not specified

Chemotherapy:
 No prior chemotherapy

Endocrine therapy:
 Not specified

Radiotherapy:
 No prior radiotherapy

Surgery:
 See Disease Characteristics

Patient Characteristics:

Age:
 30 and under

Performance status:
 ECOG 0-2

Life expectancy:
 Not specified

Hematopoietic:
 Absolute neutrophil count at least 1,000/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin no greater than 1.5 times normal
 SGOT no greater than 3 times normal

Renal:
 Creatinine normal
 Phosphate at least 3.0 mg/dL without supplementation

Cardiovascular:
 Shortening fraction at least 28% by echocardiogram
 If echocardiogram unsatisfactory, must have ejection fraction at least 50%
 No history of pericarditis or myocarditis
 No symptomatic arrhythmia or symptomatic cardiac conduction disturbances

Expected Enrollment

Approximately 180 patients will be accrued for this study within 2 years.

Outline

This is a multicenter study.  Patients are enrolled sequentially on 1 of 3 
pilot intensification regimens.  After surgery to completely remove the 
primary tumor, patients are assigned to 1 of 2 adjuvant chemotherapy groups 
based on percent necrosis at limb salvage.

Pilot 1:  (Closed to accrual as of 6/2/2000)  Patients receive dexrazoxane IV 
followed immediately by doxorubicin IV over 20 minutes plus cisplatin IV over 
4 hours on days 1 and 2 of weeks 1 and 6.  Methotrexate IV over 4 hours is 
administered on day 1 of weeks 4, 5, 9, and 10.  Patients undergo surgery on 
week 11.  Adjuvant chemotherapy begins on day 1 of week 13.
      Group 1 (good response to neoadjuvant chemotherapy):  Patients receive 
 methotrexate IV over 4 hours every 3 weeks for 6 courses, beginning on week
 13.  Patients also receive dexrazoxane and doxorubicin every 3 weeks for 4
 courses, beginning on week 14.  Cisplatin is administered with the first 2
 courses of dexrazoxane and doxorubicin.
      Group 2 (standard response to neoadjuvant chemotherapy):  Patients
 receive methotrexate and cisplatin as in group 1 plus dexrazoxane and
 doxorubicin for 6 courses.

Pilot 2:  Patients receive preoperative therapy comprised of dexrazoxane, 
doxorubicin, and methotrexate as in pilot 1.  Ifosfamide IV over 4 hours is 
also administered on days 1-5 of week 1.  Patients undergo surgery on week 11, 
then begin adjuvant chemotherapy on week 13.
      Group 1:  Patients receive methotrexate, dexrazoxane, and doxorubicin as
 in pilot 1, group 1.  Ifosfamide is also administered on weeks 14 and 20. 
 Cisplatin is administered on weeks 17, 23, and 26.
      Group 2:  Patients receive methotrexate, dexrazoxane, and doxorubicin as
 in pilot 1, group 2.  Ifosfamide is administered on weeks 14, 20, 26, and 31. 
  Cisplatin is administered on weeks 17, 23, and 29.

Pilot 3:  (Open to accrual as of 6/2/2000)  Patients receive preoperative 
therapy comprised of methotrexate, dexrazoxane, doxorubicin, ifosfamide, and 
cisplatin as in pilot 2.  Patients undergo surgery on week 11, then begin 
adjuvant chemotherapy on week 13. 
      Group 1:  Patients receive methotrexate, dexrazoxane, doxorubicin,
 ifosfamide, and cisplatin as in pilot 2, group 1.  
      Group 2:  Patients receive methotrexate on weeks 13, 19, 29, 32, 35, and
 36, high dose ifosfamide and etoposide IV over 4 hours on days 1-5 of weeks
 14, 23, and 26, and cisplatin on weeks 20, 30, and 33.  Dexrazoxane and
 doxorubicin are administered on weeks 17, 20, 30, and 33.

Patients are followed every 3 months for 1 year, every 6 months for 4 years 
and then annually thereafter.

Janeway KA, Barkauskas DA, Krailo MD, et al.: Outcome for adolescent and young adult patients with osteosarcoma: A report from the Children's Oncology Group. Cancer : , 2012.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Cindy Schwartz, MD, Protocol chair (Contact information may not be current)		Ph: 410-955-8964

Registry Information
Official Title		Protocol for Patients with Newly-Diagnosed Non-Metastatic Osteosarcoma - A POG/CCG Pilot Intergroup Study
Trial Start Date		1999-09-15
Registered in ClinicalTrials.gov		NCT00003937
Date Submitted to PDQ		1999-06-17
Information Last Verified		2012-01-27
NCI Grant/Contract Number		U10-CA13539, U10-CA30969

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