A Phase I/II Study of Escalating Doses of SU5416 (NSC 696819) in Combination With CPT-11 in Patients With Advanced Colorectal Carcinoma

Inclusion Criteria:

- Patients must have histologically confirmed adenocarcinoma of the colon or rectum

- Patients must have locally advanced or metastatic disease not amendable to
potentially curative treatment

- Patients must have an ECOG performance status of 0-2

- Men and women of any racial and ethnic group

- Absolute neutrophil count (neutrophils + bands) of >= 1,500/ul

- Platelet count of >= 100,000/ul

- Patients must have a serum creatinine of =< 1.5 mg/dL or a calculated creatinine
clearance >= 60 mL/min

- Serum bilirubin =< 1.5 mg/dL, regardless of whether patients have liver involvement
secondary to tumor

- SGOT must be =< 3 times institutional upper limit of normal

- Patients must be fully recovered from any previous surgery (at least 4 weeks from
major surgery)

- Patients must have recovered from prior radiation therapy (at least 4 weeks from
radiation)

- Fertile patients (male and female) must agree to use a medically effective
contraceptive method throughout the treatment period and for 3 months following
cessation of treatment

- Patients must provide written informed consent

- Patients must have either measurable or evaluable disease; measurable disease is
defined as at least one bidimensionally measurable lesion >= 1 x 1 cm that is outside
the field of any prior radiation therapy

- In Phase I: Patients with a history of a prior malignancy are eligible for treatment

- In Phase II: Patients who have undergone potentially curative therapy for a prior
malignancy and who have had no evidence of that disease for > 5 years are eligible
for treatment; adequately treated basal cell or squamous cell skin cancer does not
apply

- In the Phase I portion of the study the following eligibility criteria must be met:

- Patients must have received no more than two prior chemotherapy regimens (one of
which must have contained a fluorinated pyrimidine) for locally advanced or
metastatic disease; if a patient progressed while on or within 6 months of
adjuvant therapy, the adjuvant regimen will be considered as treatment for
metastatic disease

- In the Phase II portion of the study the following eligibility criteria must be met:

- Patients must have received one and only one prior chemotherapy regimen, which
must have contained a fluorinated pyrimidine, for treatment of locally advanced
or metastatic disease; if a patient progressed while on or within 6 months of
adjuvant therapy, the adjuvant regimen will be considered as treatment for
metastatic disease

Exclusion Criteria:

- Patients who have previously received SU5416, CPT-11, or any topoisomerase I
inhibitor

- Patients with uncompensated coronary artery disease on electrocardiogram or physical
examination, or with a history of myocardial infarction, or severe/unstable angina in
the past 6 months are not eligible

- Patients with diabetes mellitus with severe peripheral vascular disease and patients
who have had a deep venous or arterial thrombosis (including pulmonary embolism)
within 3 months of entry are not eligible

- Patients with known allergy to Cremaphor, or Cremophor-based drug products

- Patients with any active or uncontrolled infection

- Patients with psychiatric disorders that would interfere with consent or follow-up

- CPT-11 is known to have teratogenic potential and may be excreted in milk; the
current SU5416 Investigator's Brocure indicates that teratogenicity studies have not
yet been performed; however, other antiangiogenesis drugs, such as thalidomide, are
known to have teratogenic potential; based on the available data, there is potential
for significant risk to a developing fetus or breast-feeding child; therefore,
pregnant women, women who are breast-feeding, and fertile men and women, unless
utilizing birth control are excluded from this study; a negative pregnancy test must
be documented during the screening period for women of childbearing potential

- Patients with either a prior history of or clinically apparent central nervous system
metastases or leptomeningeal carcinomatosis disease

- Patients with a history of seizures or who are receiving phenytoin, phenobarbital, or
other antipileptic prophylaxis

- Patients with uncontrolled diabetes mellitus

- Patients with known Gilbert's Disease (may have excessive CPT-11-induced toxicity)

- Patients with any other severe concurrent disease which in the judgement of the
investigator would make the patient inappropriate for the study

- Patients who have received any investigational drug =< 30 days prior to enrollment