Osteosarcoma is the most common bone cancer in children. Survival rates for osteosarcoma have greatly improved over the years. Most patients who receive surgery and chemotherapy can look forward to long-term remission (disease-free state). Previous studies have shown that chemotherapy (cancer-fighting drugs) along with surgery to remove the tumor and surrounding tissue is an effective treatment for osteosarcoma. Survival rates of patients who receive surgery without chemotherapy are about 20 percent. Chemotherapy can be effective in killing tumor cells, reducing tumor size, and preventing the spread of tumor to other parts of the body. St. Jude Children’s Research Hospital researchers want to determine which drugs are most effective in treating osteosarcoma. They also want to limit side effects as much as possible.

Osteosarcoma is the most common bone cancer in children. Survival rates for osteosarcoma have greatly improved over the years. Most patients who receive surgery and chemotherapy can look forward to long-term remission (disease-free state). Previous studies have shown that chemotherapy (cancer-fighting drugs) along with surgery to remove the tumor and surrounding tissue is an effective treatment for osteosarcoma. Survival rates of patients who receive surgery without chemotherapy are about 20 percent. Chemotherapy can be effective in killing tumor cells, reducing tumor size, and preventing the spread of tumor to other parts

of the body. St. Jude Children’s Research Hospital researchers want to determine which drugs are most effective in treating osteosarcoma. They also want to limit side effects as much as possible.

In 1986, St. Jude Children’s Research Hospital researchers initiated a trial (OS86) of ifosfamide, cisplatin, doxorubicin, and high-dose methotrexate. The subsequent trial (OS91), which was completed in 1997, substituted carboplatin for cisplatin. The 5-year survival estimates for patients with localized osteosarcoma were 69.2%±7.4% for those treated on OS86 and 73.1%±7.0% for those treated on OS91 (P=0.84). The results of OS91 demonstrated that the carboplatin and ifosfamide combination has substantial antitumor activity. When used with doxorubicin and high-dose methotrexate to treat localized osteosarcoma, this combination yielded outcomes comparable to those of trials using cisplatin-based therapy, with less long-term toxicity. The OS91 study also showed that dynamic contrast-enhanced MR imaging may be useful in predicting tumor response.

On the basis of these results and the results of other studies that have eliminated high-dose methotrexate, St. Jude Children’s Research Hospital researchers are conducting a trial (OS99) to evaluate ifosfamide, carboplatin, and doxorubicin in an up-front window before surgery for localized and resectable osteosarcoma. High-dose methotrexate, which may interfere with the dose-intensive delivery of other agents, has been eliminated from OS99.

In 1986, St. Jude Children’s Research Hospital researchers initiated a trial (OS86) of ifosfamide, cisplatin, doxorubicin, and high-dose methotrexate. The subsequent trial (OS91), which was completed in 1997, substituted carboplatin for cisplatin. The 5-year survival estimates for patients with localized osteosarcoma were 69.2%±7.4% for those treated on OS86 and 73.1%±7.0% for those treated on OS91 (P=0.84). The results of OS91 demonstrated that the carboplatin and ifosfamide combination has substantial antitumor activity. When used with doxorubicin and high-dose methotrexate to treat localized osteosarcoma, this combination yielded outcomes comparable to those of trials using cisplatin-based therapy, with less long-term toxicity. The OS91 study also showed that dynamic contrast-enhanced MR imaging may be useful in predicting tumor response.

On the basis of these results and the results of other studies that have eliminated high-dose methotrexate, St. Jude Children’s Research Hospital researchers are conducting a trial (OS99) to evaluate ifosfamide, carboplatin, and doxorubicin in an up-front window before surgery for localized and resectable osteosarcoma. High-dose methotrexate, which may interfere with the dose-intensive delivery of other agents, has been eliminated from OS99.

Condition	Intervention	Phase
Osteosarcoma	Drug: Isofamide, Carboplatin, Doxorubicin  Procedure: Limb Sparing	Phase II Phase III

Further Study Details: 

Primary Outcomes: To compare the tumor response to chemotherapy with three drugs(ifosfamide, carboplatin, and doxorubicin)used before surgery in an earlier St.Jude Children''''s Research Hospital study.; To study the accuracy of dynamic contrast-enhanced MR imaging in assessing the degree of response.
Secondary Outcomes: To study the feasibility of administering therapy on an outpatient basis.; To study whether a 3-cm surgical margin of normal bone (rather than the 5-cm standard margin)provides satisfactory; resection of the primary tumor.; To study biological markers including telomerase activity and DNA index.; To learn what subjects and parents think about the of life during and after treatment
Expected Total Enrollment:  70

Ages Eligible for Study:  up to  25 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• All subjects with histologically proven high-grade osteosarcoma,chondrosarcoma, MFH, fibrosarcoma or chondrosarcoma of bone, whose tumors are potentially resectable (either by limb sparing, en bloc resection, or amputation) and have no evidence of metastasis.
• Adequate liver, renal and cardiac function.
• Age: Younger than 25 years old

Exclusion Criteria:

• Prior chemotherapy

Please refer to this study by ClinicalTrials.gov identifier  NCT00145639

Najat C Daw, MD      1-866-278-5833    najat.daw@stjude.org

Tennessee
      St.Jude Children''''s Research Hospital, Memphis,  Tennessee,  38105,  United States; Recruiting

Study chairs or principal investigators

Najat C Daw, MD,  Principal Investigator,  St. Jude Children''''s Research Hospital   

Study ID Numbers:  OS99
Last Updated:  September 2, 2005
Record first received:  September 1, 2005
ClinicalTrials.gov Identifier:  NCT00145639
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-09-06