- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00119301
Methotrexate, Trimetrexate Glucuronate, and Leucovorin in Treating Patients With Refractory or Recurrent Osteosarcoma
Phase I Study of High Dose Methotrexate With Simultaneous Trimetrexate and Leucovorin in Patients With Recurrent Osteosarcoma
RATIONALE: Drugs used in chemotherapy, such as methotrexate, trimetrexate glucuronate, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of trimetrexate glucuronate when given together with methotrexate and leucovorin in treating patients with refractory or recurrent osteosarcoma.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
Maximum tolerated dose (MTD) after 1 course of treatment
|
Dose-limiting toxicities as assessed by hematology and biochemistry testing on days 1, 8, and 28 of each course
|
Secondary Outcome Measures
Outcome Measure |
---|
Antitumor activity as measured by radiographic response using RECIST criteria after every 2 courses of treatment
|
Antitumor activity as measured by pathologic response using the Huvos grading system to evaluate post-treatment tumor necrosis at time of tumor resection after completion of study treatment
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Bone Tissue
- Neoplasms, Connective Tissue
- Sarcoma
- Osteosarcoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Dermatologic Agents
- Micronutrients
- Vitamins
- Calcium-Regulating Hormones and Agents
- Antifungal Agents
- Reproductive Control Agents
- Antidotes
- Vitamin B Complex
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Leucovorin
- Calcium
- Levoleucovorin
- Methotrexate
- Trimetrexate
Other Study ID Numbers
- 05-028
- MSKCC-IRB-05028
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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