A Phase I Study of SU5416, an Antiangiogenesis Agent, in Combination With Carboplatin in Patients With Platinum-Refractory Ovarian Cancer

Inclusion Criteria

Must have histopathologically documented epithelial ovarian carcinoma confirmed in the
Laboratory of Pathology, at the National Cancer Institute prior to starting this study.
Also eligible will be patients with the histologic diagnosis of: Recurrent primary
fallopian tube cancers; Recurrent primary peritoneal cancers (non-mesothelioma).

Must have either measurable disease by physical exam or radiographic imaging, or patients
must have evaluable disease. Evaluable disease will include patients with third-space
fluid accumulations that are proven to be positive for adenocarcinoma; and patients with
an elevated CA125 above 100 IU per mL.

Must have platinum-refractory disease (persistent or recurrent disease within 6 months of
last cisplatin or carboplatin therapy).

Must have a life expectancy of more than 2 months.

Must have an ECOG performance status of 0, 1, or 2.

No patients with medical or surgical complications requiring immediate intervention, but
may enroll after resolution of the acute problem (e.g. impending bowel obstruction, active
infection, etc.).

PT and PTT must be less than 1.5 times the upper limit of normal.

Must have recovered from any toxicity related to prior therapy to NCI/CTEP Grade 0, or 1,
with the exception of peripheral neuropathy, in which case grade 2 toxicity is
permissible.

Granulocyte count must be greater than or equal to 1,500/mm(3).

Hemoglobin must be greater than or equal to 9.0 g/dL (pre-treatment transfusion is
allowed, provided the hemoglobin is maintained for more than seven days and/or active
source of bleeding is identified and treated).

Platelet count must be greater than or equal to 100,000/mm(3).

Acute care panel (electrolytes, BUN) and urinalysis should be considered normal for each
patient in the judgement of the clinic attending (blood glucose is excluded from this
evaluation). No gross abnormalities should be present. "Normal" will be defined as the
normal range for that test in the facility where the test was taken.

Hepatic function: normal bilirubin (total); ALT less than 2 times the upper limit of
normal; AST less than 2 times the upper limit of normal.

Must be capable of understanding and signing an informed consent form.

Must be willing to travel from their home to the NIH for follow-up visits.

Must be greater than or equal to 18 years of age.

Must be able and willing to follow instructions and conform to protocol.

Prior chemotherapy must have been stopped at least 4 weeks prior to enrollment. Mitomycin
C and nitrosoureas should have been stopped at least 6 weeks prior to enrollment.

Must have failed no more than three prior chemotherapy regimens. Retreatment of patients
who were initially sensitive to platinum with either the same regimen or platinum as a
single agent would only constitute one prior regimen.

No history of external beam radiation.

Patients capable of childbearing must use effective birth control while on the study.

No non-skin malignancy or melanoma within the past 5 years.

No active infection, including positive serology for HIV. Patients on suppressive
antibiotic therapy will be evaluated on a case-by-case basis.

No history of brain metastases.

No uncompensated coronary artery disease on electrocardiogram or physical examination, or
a history of myocardial infarction or severe/unstable angina in the past 6 months. No
diabetes mellitus with severe peripheral vascular disease and no deep venous or arterial
thrombosis (including pulmonary embolism) within 3 months of entry. No New York class
II-IV congestive heart failure, chronic obstructive lung disease requiring oxygen therapy
or medication, or uncontrolled seizure activity. Uncomplicated asthma will be allowed.
No active therapy for angina.

Must not have undergone a bone marrow transplant regimen.

No pregnant or breastfeeding individuals.

Must not have non-cancer life-threatening illnesses, including untreated infection (must
be at least 1 week off antibiotic therapy before beginning cycle 1 of SU5416).

No non-epithelial histologies.

No peripheral neuropathy, NCI CTEP grade 3 or 4.