AG2037 in Treating Patients With Advanced, Metastatic, or Recurrent Solid Tumors

The University of Alabama at Birmingham

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: pelitrexol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00017524

NCI-G01-1954

CDR0000068699

AG-2037-003-A2

UAB-F001227008

UAB-0052

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of AG2037 in treating patients who have advanced, metastatic, or recurrent solid tumors.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxic effects of AG2037 in patients with advanced, metastatic, or recurrent solid tumor.
• Determine the safety and tolerance of this drug in these patients.
• Assess the pharmacokinetics of this drug in these patients.
• Document any antitumor effects of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive AG2037 IV weekly on weeks 1-3. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AG2037 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 4 weeks.

PROJECTED ACCRUAL: A total of 18-60 patients will be accrued for this study.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed solid tumor

  • Advanced, metastatic, or recurrent disease
  • No curative therapy exists

• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• WHO 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL (unless due to Gilbert's syndrome)
• SGOT OR SGPT no greater than 2 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 60 mL/min

Other:

• No unstable or severe concurrent medical condition that would preclude study participation
• No sociological or familial condition that would preclude study compliance
• No psychological or addictive disorder that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 40% of bone marrow

Surgery:

• Not specified

Other:

• At least 2 weeks since prior blood transfusions
• At least 4 weeks since prior investigational agent and recovered
• No prior glycinamide ribonucleotide formyltransferase (GARFT) inhibitor
• No concurrent extradietary folate supplements
• No concurrent allopurinol
• No other concurrent anticancer or investigational agents