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


Phase 2
N/A
30 Years
Not Enrolling
Both
Metastatic Osteosarcoma

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility and safety of treatment assessed using CTC version 2.0

Outcome 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 Time Frame:

Up to 6 years

Safety Issue:

Yes

Principal Investigator

David Ebb

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01863

NCT ID:

NCT00023998

Start Date:

July 2001

Completion Date:

May 2007

Related Keywords:

  • Metastatic Osteosarcoma
  • Osteosarcoma

Name

Location

Children's Oncology GroupArcadia, California  91006-3776