NCT00145639

Osteosarcoma1999-A Study Of Intensive Chemotherapy for Osteosarcoma

Osteosarcoma 1999-A Study Of Intensive Chemotherapy Utilizing Ifosfamide, Carboplatin, and Doxorubicin for Adjuvant Chemotherapy for Treatment of Osteosarcoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 25 Years
• Healthy volunteers: Not accepted

Summary

This trial (OS99) evaluates the use of 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, is eliminated from the treatment of localized disease. The primary objective is to compare the response rate of pre-surgical chemotherapy comprised of ifosfamide, doxorubicin, and carboplatin to that obtained with ifosfamide and carboplatin in the St. Jude OS-91 trial for patients with non-metastatic resectable osteosarcoma. We hypothesize that the histologic response rate will be improved by the addition of one course of pre-operative chemotherapy on this trial compared to the previous OS-91 trial.

Detailed description

This study has multiple research objectives: * To compare the response rate of pre-surgical chemotherapy comprised of ifosfamide, doxorubicin, and carboplatin to that obtained with ifosfamide and carboplatin in the St. Jude OS-91 trial for patients with non-metastatic resectable osteosarcoma * To continue the evaluation of dynamic contrast-enhanced magnetic resonance imaging (DEMRI) in predicting tumor response and accurately assessing the degree of response (continued from OS-91). * To determine the feasibility of delivering outpatient-based chemotherapy for osteosarcoma using ifosfamide-doxorubicin-carboplatin. * To determine whether resection of the primary site may be satisfactorily performed with a 3 cm margin of normal bone (rather than 5 cm). * To study biologic and biochemical characteristics of the tumor cells that may be of prognostic significance * To study the patients' and parents' perspectives of the patients' quality of life during and after treatment. Description of Treatment Plan: This study employs the following treatment strategy: neoadjuvant chemotherapy followed by definitive surgery for local control and adjuvant chemotherapy after tumor resection. Pre-operative chemotherapy phase (weeks 0-12): Three courses of ifosfamide/carboplatin given every 3 weeks followed by one 3-week course of doxorubicin.Disease evaluation is performed after 3 courses and after 4 courses of chemotherapy. Weeks 0, 3, and 6 - Ifosfamide-Carboplatin Ifosfamide: 2.65 gm/m2 IV daily over 15-30 minutes x 3 (Days 1, 2, 3) with MESNA. Carboplatin: dose based on GFR and targeted to an AUC of 8 mg/mL/min, given IV over 1 hour (Day 1 only) Week 9- Evaluation, followed by Doxorubicin Doxorubicin: 25 mg/m2 IV over 1 hour, daily x 3 Week 12 Evaluation followed by definitive Surgery Local control by amputation or limb-salvage procedure Post-operative chemotherapy (Weeks 14-35) Ifosfamide, carboplatin, and doxorubicin in two-agent pairs for approximately 35 weeks. Week 14 - Ifosfamide-Doxorubicin Ifosfamide: 2.65 gm/m2 IV daily over 15-30 minutes x 3 (Days 1, 2, 3) with MESNA, Doxorubicin: 25 mg/m2 IV over 1 hour, daily x 2 (Days 1 and 2) Week 17 - Ifosfamide-Carboplatin Ifosfamide: 2.65 gm/m2 IV daily over 15-30 minutes x 3 (Days 1, 2, 3) with MESNA, Carboplatin: targeted to an AUC of 8 mg/mL/min given IV over 1 hour (Day 1 only) Week 20 - Carboplatin-Doxorubicin Carboplatin: targeted to an AUC of 8 mg/mL/min given IV over 1 hour (Day 1 only), Doxorubicin: 25 mg/m2 IV over 1 hour, daily x 2 (Days 1 and 2) Week 23 - Evaluation, followed by Ifosfamide: Doxorubicin. Ifosfamide: 2.65 gm/m2 IV daily over 15-30 minutes x 3 (Days 1, 2, 3) with MESNA, Doxorubicin: 25 mg/m2 IV over 1 hour, daily x 2 (Days 1 and 2) Week 26 - Ifosfamide-Carboplatin Ifosfamide: 2.65 gm/m2 IV daily over 15-30 minutes x 3 (Days 1, 2, 3) with MESNA, Carboplatin: targeted to an AUC of 8 mg/mL/min given IV over 1 hour (Day 1 only) Week 29 - Carboplatin-Doxorubicin Carboplatin: targeted to an AUC of 8 mg/mL/min given IV over 1 hour (Day 1 only), Doxorubicin: 25 mg/m2 IV over 1 hour, daily x 2 (Days 1 and 2) Week 32 - Evaluation, followed by Ifosfamide-Doxorubicin. Ifosfamide: 2.65 gm/m2 IV daily over 15-30 minutes x 3 (Days 1, 2, 3) with MESNA, Doxorubicin: 25 mg/m2 IV over 1 hour, daily x 2 (Days 1 and 2) Week 35 - Carboplatin-Doxorubicin Carboplatin: targeted to an AUC of 8 mg/mL/min given IV over 1 hour (Day 1 only), Doxorubicin: 25 mg/m2 IV over 1 hour, daily x 2 (Days 1 and 2)

Conditions

• Osteosarcoma

Interventions

Type	Name	Description
DRUG	Ifosfamide, Carboplatin, Doxorubicin	See Detailed Description for treatment plan.
PROCEDURE	Limb Sparing	See Detailed Description for treatment plan.

Timeline

• Start date: 1999-05-01
• Primary completion: 2006-05-01
• Completion: 2006-05-01
• First posted: 2005-09-05
• Last updated: 2011-06-10

Locations

4 sites across 2 countries: United States, Chile