Osteosarcoma1999-A Study Of Intensive Chemotherapy for Osteosarcoma

This study has been completed.
Sponsor:
Collaborators:
Immunex/Berlex
Information provided by:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00145639
First received: September 1, 2005
Last updated: June 8, 2011
Last verified: June 2011

September 1, 2005
June 8, 2011
May 1999
May 2006   (final data collection date for primary outcome measure)
Histologic response rate [ Time Frame: After all patients have undergone definitive surgery and become evaluable for histologic response evaluation. ]
  • 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.
Complete list of historical versions of study NCT00145639 on ClinicalTrials.gov Archive Site
Not Provided
  • 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
Not Provided
Not Provided
 
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

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.

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)

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Osteosarcoma
  • Drug: Ifosfamide, Carboplatin, Doxorubicin
    See Detailed Description for treatment plan.
  • Procedure: Limb Sparing
    See Detailed Description for treatment plan.
1
Interventions:
  • Drug: Ifosfamide, Carboplatin, Doxorubicin
  • Procedure: Limb Sparing

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
May 2006
May 2006   (final data collection date for primary outcome measure)

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
Both
up to 25 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Chile
 
NCT00145639
OS99
Yes
Fariba Navid, M.D., St.Jude Children's Research Hospital
St. Jude Children's Research Hospital
  • Immunex/Berlex
  • National Institutes of Health (NIH)
Principal Investigator: Fariba Navid, MD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP