An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors

Inclusion Criteria:

- Histologically or cytologically confirmed locally advanced or metastatic solid tumor

- Refractory to standard therapy or for which there is no standard therapy

- Preference given to colorectal cancer, upper gastrointestinal cancer, or
neuroendocrine tumors

- Evaluable disease

- No CNS metastases or primary CNS malignancy

- Performance status - Karnofsky 60-100%

- WBC at least 3,500/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin no greater than 1.5 mg/dL

- AST and ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if
liver metastases are present)

- Creatinine no greater than 1.5 mg/dL

- No history of cardiac arrhythmia

- No congestive heart failure

- No myocardial infarction within the past 6 months

- No prior grade 3 or 4 diarrhea secondary to irinotecan, despite optimal
antidiarrheal prophylaxis

- HIV negative

- No serious or uncontrolled infection

- No other medical condition or reason that would preclude study participation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 2 months
after study participation

- At least 2 weeks since prior immunotherapy

- No more than 2 prior chemotherapy regimens unless there is no evidence of significant
myelotoxicity as determined by the primary investigator

- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)

- Prior irinotecan and fluorouracil allowed

- At least 2 weeks since prior radiotherapy

- Recovered from all prior therapy

- No other concurrent investigational medications

- No concurrent vitamins, antioxidants, or herbal preparations or supplements except a
single daily multivitamin