Expired Study
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Arcadia, California 91006


Purpose:

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


Study summary:

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.


Criteria:

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


Study is Available At:


Original ID:

NCI-2012-01863


NCT ID:

NCT00023998


Secondary ID:

AOST0121


Study Acronym:


Brief Title:

Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma


Official Title:

A Groupwide Phase II Study of Trastuzumab (Herceptin) in Metastatic Osteosarcoma Patients With Tumors That Overexpress HER2


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

N/A


Maximum Age:

30 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety/Efficacy Study, I


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

80


Enrollment Type:

Actual


Overall Contact Information

Official Name:David Ebb
Principal Investigator
Children's Oncology Group

Study Dates

Start Date:July 2001
Completion Date:May 2007
Primary Completion Date:November 2005
Primary Completion Type:Actual
Verification Date:January 2013
Last Changed Date:February 1, 2013
First Received Date:September 13, 2001

Study Outcomes

Outcome Type:Primary Outcome
Measure:Feasibility and safety of treatment assessed using CTC version 2.0
Time Frame:Up to 6 years
Safety Issues:True
Description:Descriptive statistics will be utilized to assess feasibility and safety. All toxicities will be carefully monitored. A detailed tabulation of observed toxicities will be made and a qualitative decision on the feasibility will be made.
Outcome Type:Primary Outcome
Measure:Response rate
Time Frame:Up to 6 years
Safety Issues:False
Description:Will be estimated with a maximum standard error of no more than 8%.
Outcome Type:Primary Outcome
Measure:Event free survival (EFS)
Time Frame:3 years
Safety Issues:False
Description:Will be estimated by the Kaplan-Meier method with a maximum standard error of 8%.

Study Interventions

Intervention Type:Drug
Name:doxorubicin hydrochloride
Description:Given IV
Arm Name:Treatment (combination chemotherapy)
Other Name:ADM
Intervention Type:Drug
Name:cisplatin
Description:Given IV
Arm Name:Treatment (combination chemotherapy)
Other Name:CACP
Intervention Type:Drug
Name:methotrexate
Description:Given IV
Arm Name:Treatment (combination chemotherapy)
Other Name:amethopterin
Intervention Type:Drug
Name:leucovorin calcium
Description:Given IV or orally
Arm Name:Treatment (combination chemotherapy)
Other Name:CF
Intervention Type:Biological
Name:filgrastim
Description:Given IV
Arm Name:Treatment (combination chemotherapy)
Other Name:G-CSF
Intervention Type:Procedure
Name:therapeutic conventional surgery
Description:Undergo resection
Arm Name:Treatment (combination chemotherapy)
Intervention Type:Radiation
Name:radiation therapy
Description:Undergo radiotherapy
Arm Name:Treatment (combination chemotherapy)
Other Name:irradiation
Intervention Type:Drug
Name:etoposide
Description:Given IV
Arm Name:Treatment (combination chemotherapy)
Other Name:EPEG
Intervention Type:Drug
Name:ifosfamide
Description:Given IV
Arm Name:Treatment (combination chemotherapy)
Other Name:Cyfos
Intervention Type:Biological
Name:trastuzumab
Description:Given IV
Arm Name:Treatment (combination chemotherapy)
Other Name:anti-c-erB-2
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Treatment (combination chemotherapy)

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (combination chemotherapy)
Description:See detailed description.

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Isakoff MS, Barkauskas DA, Ebb D, Morris C, Letson GD. Poor Survival for Osteosarcoma of the Pelvis: A Report from the Children's Oncology Group. Clin Orthop Relat Res. 2012 Feb 22. [Epub ahead of print]
PMID:22354612
Reference Type:Reference
Citation:Janeway KA, Barkauskas DA, Krailo MD, Meyers PA, Schwartz CL, Ebb DH, Seibel NL, Grier HE, Gorlick R, Marina N. Outcome for adolescent and young adult patients with osteosarcoma: A report from the Children's Oncology Group. Cancer. 2012 Jan 17; [Epub ahead of print]
PMID:22252521
Reference Type:Results Reference
Citation:Ebb D, Meyers P, Grier H, Bernstein M, Gorlick R, Lipshultz SE, Krailo M, Devidas M, Barkauskas DA, Siegal GP, Ferguson WS, Letson GD, Marcus K, Goorin A, Beardsley P, Marina N. Phase II Trial of Trastuzumab in Combination With Cytotoxic Chemotherapy for Treatment of Metastatic Osteosarcoma With Human Epidermal Growth Factor Receptor 2 Overexpression: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Jun 4. [Epub ahead of print]
PMID:22665540

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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