Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00023998
First received: September 13, 2001
Last updated: February 1, 2013
Last verified: January 2013
  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


Condition Intervention Phase
Metastatic Osteosarcoma
Drug: doxorubicin hydrochloride
Drug: cisplatin
Drug: methotrexate
Drug: leucovorin calcium
Biological: filgrastim
Procedure: therapeutic conventional surgery
Radiation: radiation therapy
Drug: etoposide
Drug: ifosfamide
Biological: trastuzumab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Groupwide Phase II Study of Trastuzumab (Herceptin) in Metastatic Osteosarcoma Patients With Tumors That Overexpress HER2

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Feasibility and safety of treatment assessed using CTC version 2.0 [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Response rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Will be estimated with a maximum standard error of no more than 8%.

  • Event free survival (EFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Will be estimated by the Kaplan-Meier method with a maximum standard error of 8%.


Enrollment: 80
Study Start Date: July 2001
Estimated Study Completion Date: May 2007
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy)
See detailed description.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given IV or orally
Other Names:
  • CF
  • CFR
  • LV
Biological: filgrastim
Given IV
Other Names:
  • G-CSF
  • Neupogen
Procedure: therapeutic conventional surgery
Undergo resection
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00023998

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: David Ebb Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00023998     History of Changes
Other Study ID Numbers: NCI-2012-01863, AOST0121, U10CA098543, CDR0000068882
Study First Received: September 13, 2001
Last Updated: February 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Osteosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Sarcoma
Doxorubicin
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Trastuzumab
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antibiotics, Antineoplastic
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 22, 2014