Combination Chemotherapy and Surgery in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma

June 20, 2013 updated by: Memorial Sloan Kettering Cancer Center

A Phase II Window Study of Trimetrexate With Simultaneous Leucovorin Protection in the Treatment of Newly Diagnosed Patients With Metastatic Osteosarcoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug or combining chemotherapy with surgery may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and surgery in treating patients who have newly diagnosed metastatic osteosarcoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Determine the efficacy of oral trimetrexate glucuronate with simultaneous leucovorin calcium protection in patients with newly diagnosed metastatic osteogenic sarcoma. II. Evaluate the toxicity of this regimen when administered prior to and following standard chemotherapy in patients with osteogenic sarcoma. III. Correlate response with in vitro determinants of chemotherapy resistance in tumor samples obtained from these patients.

OUTLINE: Patients receive induction therapy of oral trimetrexate glucuronate (TMTX) and leucovorin calcium every 12 hours for 21 days (weeks 0-2). Patients receive leucovorin calcium for 3 additional days after the last dose of TMTX. If age prevents compliance with oral administration, patients receive TMTX IV and leucovorin calcium IV. Patients undergo definitive surgery 7-10 days after the induction therapy (week 4). Patients undergo surgery for metastatic disease, if indicated, as soon as possible following recovery from definitive surgery. Patients then receive maintenance therapy every 3 weeks for 8-9 months according to the following schedule: Patients receive ifosfamide IV over 1 hour 4 times daily on days 1-4 plus doxorubicin IV over 48 hours on days 1-2 in weeks 6, 14, and 22, and ifosfamide alone in week 30. Patients receive cisplatin IV over 4 hours for 1 day, plus doxorubicin IV over 48 hours for 2 days beginning on the same day as the first dose of cisplatin, in weeks 10, 18, and 26. Patients receive cisplatin alone in week 34. Patients receive filgrastim subcutaneously daily for 2 weeks starting 24 hours after the completion of each course of ifosfamide and cisplatin therapy. Patients receive methotrexate IV over 4 hours for 1 day, plus oral leucovorin calcium every 6 hours for at least 10 doses beginning 20 hours after the last dose of methotrexate, in weeks 9, 13, 17, 21, 25, 29, 33, and 37. In severe cases, patients receive leucovorin calcium IV over 24 hours. Patients who respond to induction therapy receive a second course of the same therapy in weeks 38-40. Patients are followed every 4 months for 1 year, then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study over 2-3 years.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Histologically confirmed, newly diagnosed (within one month of biopsy) malignant high grade osteosarcoma Must have pulmonary metastases (two or more nodules) and/or disease involving other bones or organs Must be an intent to resect at least one primary and/or metastatic site following preoperative chemotherapy Must have at least 1 evaluable site of disease No radiation induced sarcoma No osteosarcoma arising in premalignant bony lesions (e.g. Paget's disease)

PATIENT CHARACTERISTICS: Age: 30 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 3.0 times normal SGOT and/or SGPT less than 3.0 times normal Renal: Creatinine no greater than 1.5 times normal OR Creatinine clearance or radioisotope GFR greater than 70 mL/min Cardiovascular: Shortening fraction greater than 28% by echocardiogram OR Ejection fraction greater than 50% by radionuclide angiogram No history of pericarditis or myocarditis

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunomodulating agents except steroids Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: No concurrent immunomodulating agents except steroids Radiotherapy: No prior or concurrent radiotherapy Surgery: Prior biopsy only of primary or metastatic area No prior resection Other: No prior therapy for any other malignancy No concurrent co-trimoxazole

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Richard Gorlick, MD, Memorial Sloan Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1998

Primary Completion (Actual)

March 1, 2000

Study Completion (Actual)

March 1, 2000

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

August 17, 2004

First Posted (Estimate)

August 18, 2004

Study Record Updates

Last Update Posted (Estimate)

June 21, 2013

Last Update Submitted That Met QC Criteria

June 20, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98-102
  • CDR0000066905 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-G99-1507

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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