Imatinib Mesylate in Combination With Docetaxel for Advanced, Platinum-Refractory Ovarian Cancer

OUTLINE: This is a multi-center study.

Submit tumor and serum samples for central review

- Imatinib 600 mg (orally qd);

- Docetaxel 30mg/m2 (4 of 6 weeks);1 cycle = 6 weeks

- Evaluate every other cycle

Each cycle will begin only when the granulocyte count is > 1,500/mm3 and the platelet count
is > 100,000/mm3 and any other treatment-related toxicities are < grade 1. If the toxicity
is not resolved to grade 0 or 1 after three weeks, the patient will be withdrawn from the
study. For days 8, 15, and 22 patients must have an absolute neutrophil count > 1,000/mm3 or
greater and platelet count > 75,000/mm3. Imatinib mesylate can be administered if platelets
>20,000 and ANC >500.

ECOG performance status 0 or 1

Hematopoietic:·

- ANC > 1,500/mm3·

- Platelets > 100,000 mm3·

- Hgb > 8g/dl

Hepatic:·

- Albumin>3gm/dL·

- Total bilirubin < ULN·

- Maximum Alk Phos: >2.5x but < 5x ULN

Renal:·

- Creatinine < 1.5 x ULN·(by Cockroft and Gault)

Cardiovascular:·

- No grade III/IV cardiac problems as defined by the New York Heart Association Criteria.
(i.e., congestive heart failure, myocardial infarction within 6 months prior to
beginning protocol therapy)

Pulmonary:·

- Not specified

Inclusion Criteria:

- Histologically documented diagnosis of ovarian cancer, primary peritoneal
carcinomatosis or fallopian tube cancer·

- Immunohistochemical documentation of c-Kit or PDGFR expression by tumor

- At least one measurable site of disease as defined by RECIST or evidence of disease
progression by CA125 measurement

- Platinum-refractory or platinum-resistant

Exclusion Criteria:

- No prior exposure to imatinib (Gleevec®) as single agent or in combination

- No chemotherapy within 28 days (42 days for nitrosourea or mitomycin-C) prior to
being registered to protocol therapy.

- No prior radiotherapy to ³ 25 % of the bone marrow

- No known brain metastases.

- Negative pregnancy test

- No current breastfeeding

- No investigational agents within 28 days prior to protocol therapy

- No prior malignancy in the past 5 years unless the other primary malignancy is not
currently clinically significant, nor requiring active intervention, or if other
primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ

- No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic
renal disease, or active uncontrolled infection)

- No known diagnosis of human immunodeficiency virus (HIV) infection.

- No major surgery within 28 days prior to being registered to protocol therapy.

- No refractory ascites requiring drainage more frequently than once a month

- No presence of clinically significant small bowel obstruction

- No prior exposure to docetaxel (exposure to paclitaxel is allowed)

- No parenteral nutrition within 28 days prior to being registered to protocol therapy.

- No concomitant treatment with potent CYP 3A4 inhibitors (i.e., ketoconazole) is
permitted during therapy on this protocol.

- No therapeutic anticoagulation with warfarin while on study (use of low molecular
weight heparin is allowed, if necessary).

- No peripheral neuropathy > grade 1

- No history of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80.

- No serious concomitant systemic disorders incompatible with the study

- No prior malignancies with the exception of curatively treated basal or squamous
carcinoma of the skin, carcinoma in-situ of the cervix, or any other cancer for which
the patient has been disease-free for < 5 years.