Osteosarcoma1999-A Study Of Intensive Chemotherapy for Osteosarcoma

NCT ID: NCT00145639

Last Updated: 2011-06-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-05-31

Study Completion Date

2006-05-31

Brief Summary

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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

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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

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Osteosarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Group Type OTHER

Ifosfamide, Carboplatin, Doxorubicin

Intervention Type DRUG

See Detailed Description for treatment plan.

Limb Sparing

Intervention Type PROCEDURE

See Detailed Description for treatment plan.

Interventions

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Ifosfamide, Carboplatin, Doxorubicin

See Detailed Description for treatment plan.

Intervention Type DRUG

Limb Sparing

See Detailed Description for treatment plan.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Immunex/Berlex

INDUSTRY

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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St.Jude Children's Research Hospital

Principal Investigators

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Fariba Navid, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status

Washington University Medical Center

St Louis, Missouri, United States

Site Status

St.Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Hospital Luis Calvo Mackenna

Santiago, , Chile

Site Status

Countries

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United States Chile

References

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Crews KR, Stewart CF, Liu T, Rodriguez-Galindo C, Santana VM, Daw NC. Effect of fractionated ifosfamide on the pharmacokinetics of irinotecan in pediatric patients with osteosarcoma. J Pediatr Hematol Oncol. 2004 Nov;26(11):764-7. doi: 10.1097/00043426-200411000-00016.

Reference Type BACKGROUND
PMID: 15543015 (View on PubMed)

Sanders RP, Drissi R, Billups CA, Daw NC, Valentine MB, Dome JS. Telomerase expression predicts unfavorable outcome in osteosarcoma. J Clin Oncol. 2004 Sep 15;22(18):3790-7. doi: 10.1200/JCO.2004.03.043.

Reference Type BACKGROUND
PMID: 15365076 (View on PubMed)

McCarville MB, Barton EH, Cameron JR, Xiong X, Daw NC, Kaste SC, Wu S, Glass JO, Reddick WE. The cause and clinical significance of central tumor photopenia on thallium scintigraphy of pediatric osteosarcoma of the extremity. AJR Am J Roentgenol. 2007 Feb;188(2):572-8. doi: 10.2214/AJR.06.0292.

Reference Type BACKGROUND
PMID: 17242270 (View on PubMed)

Freeman SS, Allen SW, Ganti R, Wu J, Ma J, Su X, Neale G, Dalton J, Billups C, Dome JS, Daw NC, Khoury JD. Osteosarcoma tumors commonly express EGFR and harbor frequent gains at the EGFR locus and losses at the PTEN Locus. Clin Cancer Res (Submitted).

Reference Type BACKGROUND

Rivera GK, Quintana J, Villarroel M, Santana VM, Rodriguez-Galindo C, Neel MD, Velez G, Ribeiro RC, Daw NC. Transfer of complex frontline anticancer therapy to a developing country: the St. Jude osteosarcoma experience in Chile. Pediatr Blood Cancer. 2008 Jun;50(6):1143-6. doi: 10.1002/pbc.21444.

Reference Type BACKGROUND
PMID: 18085687 (View on PubMed)

McCarville MB, Romano E, Daw N, Xiong X, Reddick W, Kaste S. Etiology of the 201Thallium

Reference Type BACKGROUND

McCarville MB, Reddick WE, Xiong X, Kaste SC, Daw NC. Clinical significance of the 201Thallium donut-sign in primary extremity osteosarcoma. Presented at the 2006 Society of Pediatric Radiology and European Society of Paediatric Radiology's Fifth Conjoint Meeting, Montreal, Quebec, Canada, May 18-20, 2006.

Reference Type BACKGROUND

Kaste SC, Waszilycsak G, McCarville MB, Daw NC. Excess cancer mortality in pediatric thallium imaging. Presented at the 2006 Society of Pediatric Radiology and European Society of Paediatric Radiology's Fifth Conjoint Meeting, Montreal, Quebec, Canada, May 18-20, 2006.

Reference Type BACKGROUND

Freeman SS, Allen SW, Ganti R, Wu J, Ma J, Su X, Neale GA, Dalton JD, Billups CA, Dome JS, Daw NC, Khoury JD. EGFR expression and copy number gain are common in osteosarcoma. Presented at the US and Canadian Academy of Pathology Annual Meeting, San Diego, California, March 24-30, 2007.

Reference Type BACKGROUND

Reddick WE, Hoffer FA, Billups CA, Jenkins JJ, Wu J, Daw NC. Response assessment using dynamic MR imaging in non-metastatic osteosarcoma. To be presented at the ASCO Annual Meeting, Chicago, Illinois, June 2007.

Reference Type BACKGROUND

Rivera GK, Quintana J, Villarroel M, Rodríguez C, Santana VM, Ribeiro RC, Daw NC. Conduct of an international collaborative osteosarcoma trial at centers in a developed and developing country. To be presented at the ASCO Annual Meeting, Chicago, Illinois, June 2007.

Reference Type BACKGROUND

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

Other Identifiers

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OS99

Identifier Type: -

Identifier Source: org_study_id

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