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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00003776
First received: November 1, 1999
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Sarcoma
Biological: filgrastim
Drug: cisplatin
Drug: doxorubicin hydrochloride
Drug: ifosfamide
Drug: leucovorin calcium
Drug: methotrexate
Drug: trimetrexate glucuronate
Procedure: surgical procedure
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase II Window Study of Trimetrexate With Simultaneous Leucovorin Protection in the Treatment of Newly Diagnosed Patients With Metastatic Osteosarcoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Study Start Date: December 1998
Study Completion Date: March 2000
Primary Completion Date: March 2000 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00003776

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Richard Gorlick, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00003776     History of Changes
Other Study ID Numbers: 98-102, CDR0000066905, NCI-G99-1507
Study First Received: November 1, 1999
Last Updated: June 20, 2013
Health Authority: United States: Federal Government

Keywords provided by Memorial Sloan-Kettering Cancer Center:
metastatic osteosarcoma

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
Trimetrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Infective Agents
Antibiotics, Antineoplastic
Antidotes
Antifungal Agents
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

ClinicalTrials.gov processed this record on October 23, 2014