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 If the toxicity is not resolved to grade 0 or 1 after three weeks, the patient will be withdrawn from the study.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.