A Phase II, Open-Label, Multicenter Study of the GARFT Inhibitor AG2037 in Patients With Metastatic Colorectal Cancer Who Failed Treatment With a 5-Fluorouracil/Leucovorin Regimen

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or
rectum

- Stage IV or recurrent disease

- Measurable disease

- Disease progression or recurrence during or after completion of prior first-line
chemotherapy with fluorouracil and leucovorin calcium (5-FU/LV)

- Prior irinotecan or oxaliplatin as part of the 5-FU/LV regimen or as subsequent
therapy allowed

- Only 2 prior regimens for metastatic disease allowed

- One additional regimen as adjuvant therapy allowed provided patient remained
disease-free for > 6 months after completion of therapy*

- Newer, targeted investigational agents (e.g., cetuximab or bevacizumab) are not
counted as a chemotherapeutic regimen unless used in combination with a
cytotoxic regimen NOTE: *If evidence of failure occurred within < 6 months after
completion of adjuvant therapy, patients may have received only 1 additional
regimen for metastatic disease

- No active brain metastases (requiring treatment or progressing)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- More than 12 weeks

Hematopoietic

- Absolute granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

Hepatic

- AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if liver involvement
is present)

- Bilirubin ≤ 1.5 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome)

Renal

- Creatinine ≤ 1.5 mg/dL

- Creatinine clearance ≥ 60 mL/min

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 1 month after study
participation

- No concurrent unstable or severe medical condition that would preclude study
participation

- No psychological or sociological condition, addictive disorder, or family problem
that would preclude study compliance

- No other malignancy within the past 5 years except curatively treated nonmelanoma
skin cancer or carcinoma in situ of the cervix or breast

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- More than 14 days since prior blood transfusion

Chemotherapy

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

Endocrine therapy

- Not specified

Radiotherapy

- More than 4 weeks since prior radiotherapy and recovered

- No prior radiotherapy to > 40% of bone marrow space

Surgery

- Not specified

Other

- No prior glycinamide ribonucleotide formyltransferase (GARFT) inhibitors

- More than 28 days since prior investigational agent and recovered

- No concurrent allopurinol