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Phase I Study of High Dose Methotrexate With Simultaneous Trimetrexate and Leucovorin in Patients With Recurrent Osteosarcoma


Phase 1
1 Year
35 Years
Not Enrolling
Both
Sarcoma

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Trial Information

Phase I Study of High Dose Methotrexate With Simultaneous Trimetrexate and Leucovorin in Patients With Recurrent Osteosarcoma


OBJECTIVES:

Primary

- Determine the maximum tolerated dose of trimetrexate glucuronate when administered with
high-dose methotrexate and leucovorin calcium in patients with refractory or recurrent
high-grade osteosarcoma.

Secondary

- Determine the dose-limiting toxic effects of this regimen in these patients.

- Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of trimetrexate glucuronate.

Patients receive high-dose methotrexate IV over 4 hours on days 1 and 8 and oral
trimetrexate glucuronate twice daily on days 2-6 and 9-13. Patients also receive leucovorin
calcium IV continuously over 24 hours or orally 2 or 4 times daily on days 9-14. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of trimetrexate glucuronate until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for this study within 2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed malignant osteosarcoma

- High-grade disease

- Recurrent or refractory disease after prior standard chemotherapy comprising
methotrexate, doxorubicin, cisplatin, and ifosfamide

- No low-grade osteosarcoma

- No parosteal or periosteal sarcoma

- No osteosarcoma arising in premalignant bony lesions (e.g., Paget's disease) OR in a
prior radiotherapy field

- No symptomatic or known brain or leptomeningeal involvement

PATIENT CHARACTERISTICS:

Age

- 1 to 35

Performance status

- Karnofsky 70-100% (for patients > 16 years of age)

- Lansky 70-100% (for patients ≤ 16 years of age)

Life expectancy

- At least 3 months

Hematopoietic

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

Hepatic

- Bilirubin ≤ 1.5 times normal

- AST and ALT ≤ 5 times normal

- Albumin ≥ 2 g/dL

- No clinically significant liver disease

Renal

- Creatinine ≤ 1.5 times normal OR

- Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of
normal

Cardiovascular

- Shortening fraction ≥ 27% by echocardiogram OR

- Ejection fraction ≥ 50% by gated radionuclide study

- No congestive heart failure

- No angina pectoris

- No myocardial infarction within the past year

- No uncontrolled arterial hypertension

- No uncontrolled arrhythmias

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of significant neurological or psychiatric disorder

- No active infection

- No symptomatic peripheral neuropathy ≥ grade 2

- No other serious illness or medical condition

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 7 days since prior biologic therapy

- At least 6 months since prior allogeneic stem cell transplantation AND no evidence of
active graft-versus-host disease

- No concurrent sargramostim (GM-CSF)

Chemotherapy

- See Disease Characteristics

- More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for
nitrosoureas)

Endocrine therapy

- Not specified

Radiotherapy

- See Disease Characteristics

- At least 2 weeks since prior local palliative radiotherapy (small port)

- At least 6 months since prior craniospinal radiotherapy

- At least 6 months since prior radiotherapy to ≥ 50% of the pelvis

- At least 6 weeks since prior substantial radiotherapy to the bone marrow

Surgery

- Not specified

Other

- Recovered from prior therapy

- More than 30 days since prior and no other concurrent investigational drugs

- More than 30 days since prior and no concurrent participation in another clinical
trial

- No concurrent medications that may interact with study drugs

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) after 1 course of treatment

Safety Issue:

Yes

Principal Investigator

Paul A. Meyers, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

05-028

NCT ID:

NCT00119301

Start Date:

April 2005

Completion Date:

Related Keywords:

  • Sarcoma
  • recurrent osteosarcoma
  • Osteosarcoma
  • Sarcoma

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021