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

Phase 2
30 Years
Not Enrolling

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Trial Information

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

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.

Inclusion 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

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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Richard Gorlick, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

December 1998

Completion Date:

March 2000

Related Keywords:

  • Sarcoma
  • metastatic osteosarcoma
  • Osteosarcoma
  • Sarcoma



Memorial Sloan-Kettering Cancer Center New York, New York  10021