Osteosarcoma1999-A Study Of Intensive Chemotherapy for Osteosarcoma
Overview[ - collapse ][ - ]
| Purpose | 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. |
|---|---|
| Condition | Osteosarcoma |
| Intervention | Drug: Ifosfamide, Carboplatin, Doxorubicin Procedure: Limb Sparing |
| Phase | Phase 2 |
| Sponsor | St. Jude Children's Research Hospital |
| Responsible Party | St. Jude Children's Research Hospital |
| ClinicalTrials.gov Identifier | NCT00145639 |
| First Received | September 1, 2005 |
| Last Updated | June 8, 2011 |
| Last verified | June 2011 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 1, 2005 |
|---|---|
| Last Updated Date | June 8, 2011 |
| Start Date | May 1999 |
| Estimated Primary Completion Date | May 2006 |
| Current Primary Outcome Measures | Histologic response rate [Time Frame: After all patients have undergone definitive surgery and become evaluable for histologic response evaluation.] |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Osteosarcoma1999-A Study Of Intensive Chemotherapy for Osteosarcoma |
|---|---|
| Official Title | Osteosarcoma 1999-A Study Of Intensive Chemotherapy Utilizing Ifosfamide, Carboplatin, and Doxorubicin for Adjuvant Chemotherapy for Treatment of Osteosarcoma |
| Brief 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) |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Osteosarcoma |
| Intervention | Drug: Ifosfamide, Carboplatin, Doxorubicin See Detailed Description for treatment plan. Procedure: Limb Sparing See Detailed Description for treatment plan. |
| Study Arm (s) | Other: 1 |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 80 |
| Estimated Completion Date | May 2006 |
| Estimated Primary Completion Date | May 2006 |
| Eligibility 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 |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States, Chile |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00145639 |
|---|---|
| Other Study ID Numbers | OS99 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | St. Jude Children's Research Hospital |
| Study Sponsor | St. Jude Children's Research Hospital |
| Collaborators | Immunex/Berlex National Institutes of Health (NIH) |
| Investigators | Principal Investigator: Fariba Navid, MD St. Jude Children's Research Hospital |
| Verification Date | June 2011 |
Locations[ + expand ][ + ]
| Arkansas Children's Hospital | Little Rock, Arkansas, United States, 72202 |
|---|---|
| Washington University Medical Center | St.Louis, Missouri, United States, 63110 |
| St.Jude Children's Research Hospital | Memphis, Tennessee, United States, 38105 |
| Hospital Luis Calvo Mackenna | Santiago, Chile |