Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma

NCT ID: NCT00023998

Last Updated: 2013-02-04

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

2001-07-31

Study Completion Date

2007-05-31

Brief Summary

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Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and kill them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. Phase II trial to study the effectiveness of chemotherapy with or without trastuzumab in treating patients who have metastatic osteosarcoma

Detailed Description

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PRIMARY OBJECTIVES:

I. Determine the feasibility and safety of trastuzumab (Herceptin) and chemotherapy in patients with HER2-overexpressing (2+ level of expression) metastatic osteosarcoma.

II. Determine the response rate and 3-year event-free survival of patients treated with this regimen.

III. Determine the cardiac toxicity and late effects of this regimen in these patients.

IV. Determine the response rate and 3-year event-free survival of poor-risk patients with HER2-negative tumors treated with chemotherapy without the addition of trastuzumab.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor HER2 status (positive vs negative).

Patients receive induction therapy comprising doxorubicin IV over 20 minutes followed by cisplatin IV over 4 hours on days 1 and 2 of weeks 1 and 6, and methotrexate IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. Patients also receive leucovorin calcium IV or orally every 6 hours beginning 24 hours after each methotrexate dose and continuing for at least 10 doses until methotrexate levels sufficiently decrease. Within 24-36 hours after completion of induction therapy, patients receive filgrastim (G-CSF) daily until blood counts recover.

Patients undergo resection of any remaining primary tumor and/or metastatic lesions during week 11. Patients who are unable to undergo resection receive radiotherapy between weeks 11 and 17.

Patients receive post-induction therapy comprising doxorubicin IV over 20 minutes on days 1 and 2 of weeks 17, 25, and 29; cisplatin IV over 4 hours on days 1 and 2 of weeks 17 and 25; methotrexate IV over 4 hours on day 1 of weeks 16, 20, 24, 28, 32, and 33; etoposide IV over 1 hour on days 1-5 of weeks 13, 21, and 34; and ifosfamide IV over 4 hours on days 1-5 of weeks 13, 21, 29, and 34. Patients also receive leucovorin calcium and G-CSF as in induction therapy. Patients whose tumors are found to over express HER2 (2+ level of expression) also receive trastuzumab IV over 30-90 minutes once a week for a total of 34 weeks in addition to the chemotherapy regimen.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80 patients (40 patients per stratum) will be accrued for this study within 2.5 years.

Conditions

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Metastatic Osteosarcoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (combination chemotherapy)

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Group Type EXPERIMENTAL

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

cisplatin

Intervention Type DRUG

Given IV

methotrexate

Intervention Type DRUG

Given IV

leucovorin calcium

Intervention Type DRUG

Given IV or orally

filgrastim

Intervention Type BIOLOGICAL

Given IV

therapeutic conventional surgery

Intervention Type PROCEDURE

Undergo resection

radiation therapy

Intervention Type RADIATION

Undergo radiotherapy

etoposide

Intervention Type DRUG

Given IV

ifosfamide

Intervention Type DRUG

Given IV

trastuzumab

Intervention Type BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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doxorubicin hydrochloride

Given IV

Intervention Type DRUG

cisplatin

Given IV

Intervention Type DRUG

methotrexate

Given IV

Intervention Type DRUG

leucovorin calcium

Given IV or orally

Intervention Type DRUG

filgrastim

Given IV

Intervention Type BIOLOGICAL

therapeutic conventional surgery

Undergo resection

Intervention Type PROCEDURE

radiation therapy

Undergo radiotherapy

Intervention Type RADIATION

etoposide

Given IV

Intervention Type DRUG

ifosfamide

Given IV

Intervention Type DRUG

trastuzumab

Given IV

Intervention Type BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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ADM ADR Adria Adriamycin PFS Adriamycin RDF CACP CDDP CPDD DDP amethopterin Folex methylaminopterin Mexate MTX CF CFR LV G-CSF Neupogen irradiation radiotherapy therapy, radiation EPEG VP-16 VP-16-213 Cyfos Holoxan IFF IFX IPP anti-c-erB-2 Herceptin MOAB HER2

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed high-grade osteosarcoma

* Metastatic
* Newly diagnosed
* No osteosarcoma arising in areas of Paget's disease or radiotherapy-induced sarcoma
* Presenting with at least 1 of the following:

* Bone metastases with or without lung metastases
* Bilateral lung metastases (any number of nodules)
* Unilateral lung metastases with at least 4 nodules
* Planned resection of either the primary site or a metastatic site of disease after completion of induction therapy
* Must be currently enrolled on the tumor biology study COG-P9851
* Performance status - ECOG 0-2
* Performance status - Karnofsky 50-100% (over age 10)
* Performance status - Lansky 50-100% (age 10 and under)
* Absolute neutrophil count \> 1,000/mm\^3
* Platelet count \> 100,000/mm\^3
* Bilirubin ≤ 1.5 times normal
* SGPT ≤ 3 times normal
* Creatinine ≤ 1.5 times normal
* Creatinine clearance or glomerular filtration rate ≥ 70 mL/min
* Shortening fraction ≥ 28% by echocardiogram
* Ejection fraction ≥ 50% by echocardiogram or MUGA
* No history of pericarditis, myocarditis, symptomatic arrhythmia, or conduction disturbances
* Normal organ function
* HIV negative
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No prior chemotherapy
* No prior radiotherapy
* See Disease Characteristics
Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Ebb

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Oncology Group

Arcadia, California, United States

Site Status

Countries

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United States

References

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Kopp LM, Womer RB, Schwartz CL, Ebb DH, Franco VI, Hall D, Barkauskas DA, Krailo MD, Grier HE, Meyers PA, Wexler LH, Marina NM, Janeway KA, Gorlick R, Bernstein ML, Lipshultz SE; Children's Oncology Group. Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children's Oncology Group. Cardiooncology. 2019 Oct 28;5:15. doi: 10.1186/s40959-019-0050-9. eCollection 2019.

Reference Type DERIVED
PMID: 32154021 (View on PubMed)

Other Identifiers

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AOST0121

Identifier Type: -

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000068882

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-01863

Identifier Type: -

Identifier Source: org_study_id

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