Methotrexate, Trimetrexate Glucuronate, and Leucovorin in Treating Patients With Refractory or Recurrent Osteosarcoma

NCT00119301 | Completed Phase 1

• 2 other identifiers: 05-028MSKCC-IRB-05028
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sarcoma

Keywords

recurrent osteosarcoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Interventions

leucovorin calcium DRUG

methotrexate DRUG

trimetrexate glucuronate DRUG

Eligibility Criteria

• Age: 1 Year - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Sarcoma; Osteosarcoma

Interventions

Leucovorin; Methotrexate; trimetrexate glucuronate

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Aminopterin

Study Officials

• Paul A. Meyers, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 12, 2005
• First Posted: July 13, 2005
• Study Start: April 1, 2005
• Primary Completion: April 1, 2007
• Last Updated: January 17, 2013

Record last verified: 2013-01

Locations

US (1)