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

A Phase I Dose-Escalation Study of AG2037 Administered Once Weekly for Three Weeks to Patients With Advanced Cancer

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: pelitrexol

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Francisco Robert, MD, FACP, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Study Completion (Actual): November 1, 2004

Study Registration Dates

• First Submitted: June 6, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 16, 2013
• Last Update Submitted That Met QC Criteria: December 12, 2013
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Other Study ID Numbers: CDR0000068699; UAB-0052; AG-2037-003-A2; UAB-F001227008; NCI-G01-1954