A Phase 2 Study of Oral MKC-1 in Patients With Ovarian or Endometrial Cancer

Inclusion criteria

• Provide written informed consent (and HIPAA authorization for release of protected health information, as applicable) prior to any study related assessments.
• Histologically confirmed epithelial ovarian cancer, primary peritoneal carcinomatosis, fallopian tube cancers, or endometrial cancer.
• Age > 18 years at the time of consent.
• Arm A: Ovarian Cancer Patients:

• Must have failed at least one prior platinum based and one taxane based chemotherapeutic regimen. [Platinum failure is defined as platinum-refractory (progression while receiving a platinum-containing regimen) or platinum-resistant (disease progression within 6 months from completion of platinum containing regimen)].
• Have measurable disease according to RECIST or CA 125 criteria according to GCIG (CA-125 value of > 2 xULN).
• Have no more than 3 prior regimens for their disease.

Arm B: Endometrial Cancer Patients:

• Have no more than 3 prior regimens for their disease
• Have measurable disease according to RECIST.
• ECOG performance status of 0, 1, or 2.
• The following laboratory results, within 10 days of MKC-1 administration:

• Hemoglobin greater than or equal to 90 g/L (9 g/dL)
• Absolute neutrophil count greater than or equal to 1.5 x 109/L
• Platelet count greater than or equal to 100 x 109/L
• Serum creatinine less than or equal to 1.5 x ULN (upper limit of normal)
• AST less than or equal to 2.5 x ULN
• Serum Albumin greater than or equal to 30 g/L (3.0 g/dL)
• Total bilirubin less than or equal to ULN

Exclusion criteria

• Administration of cancer specific therapy within the following periods prior to study drug initiation:

• chemotherapy less than 3 weeks prior;
• hormonal therapy less than one week prior;
• radiation therapy less than 2 weeks prior.
• Requirement for paracentesis > 2 liters/week.
• Pregnant or breast-feeding women. Female patients must be postmenopausal, surgically sterile, or they must agree to use a physical method of contraception. Female patient with childbearing potential must have a negative pregnancy test within 10 days before the first MKC-1 administration.
• Known CNS metastases unless treated, clinically stable, and not requiring steroids.
• Clinical evidence of significant bowel obstruction, active uncontrolled malabsorption syndromes, or a history of total gastrectomy.
• Uncontrolled hypercalcemia (serum calcium-corrected > 3 mmol/L [12 mg/dL]).
• Serious cardiac condition (Class III/IV congestive heart failure according to New York Heart Association classification); documented acute myocardial infarction within the previous 6 months.
• Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient. These include: infection requiring parenteral or oral anti-infective treatment, any altered mental status, or any psychiatric condition that would interfere with the understanding of the informed consent.
• Patients with previous malignancies unless free of recurrence for at least 5 years except cured basal cell carcinoma of the skin or carcinoma-in-situ of the uterine cervix.
• Treatment with antiretroviral therapy metabolized through CYP3A4 (including indinavir, nelfinavir, ritonavir and saquinavir).