A Study to Determine the Antitumor Activity and Evaluate the Safety of MKC-1

A Phase 2 Study of Oral MKC-1 Administered Twice Daily for 14 Consecutive Days Every 4 Weeks in Patients With Advanced or Metastatic Breast Cancer

This phase 2 study will determine the antitumor activity, based on the objective rate, of oral MKC-1, administered twice daily for 14 consecutive days every 4 weeks, in patients with advanced or metastatic breast carcinoma. The study will also evaluate the safety and response duration in patients, time to tumor progression, and overall survival in patients following MKC-1 therapy.

Inclusion Criteria:

• Histologically or cytologically confirmed advanced or metastatic adenocarcinoma of the breast

• 18 years or older

• Karnofsky performance status greater than or equal to 70%

• Radiographic or physical examination evidence of at least one site of unidimensionally-measurable disease, using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria

• Must have failed both a taxane and an anthracycline, given sequentially or in combination, either in an adjuvant or metastatic setting

• All acute toxicity of any prior chemotherapy, surgery or radiotherapy must have resolved to National Cancer Institute Common Toxicity Criteria (NCI CTC) Grade less than or equal to 1

• Lab results, within 10 days of MKC-1 administration:

  • Hemoglobin less than or equal to 9 g/dL
  • Absolute neutrophil count greater than or equal to 1.5 x 10^9/L
  • Platelet count greater than or equal to 75 x 10^9/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 LLN (lower limit of normal)
  • Total bilirubin less than or equal to ULN
  • Alkaline phosphatase less than or equal to 2.5 x ULN

• Signed informed consent

Exclusion Criteria:

• Pre-existing hepatomegaly with disease measures greater than or equal to 2 cm below the costal margin, secondary to malignancy

• 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

• Be pregnant or lactating; not employing effective birth control

• Known central nervous system (CNS) metastases unless treated, clinically stable and not requiring steroids

• Clinical evidence of bowel obstruction, active uncontrolled malabsorption syndromes or a history of total gastrectomy

• Administration of any investigational agent (therapeutic or diagnostic) within 4 weeks prior to receipt of study medication

• Uncontrolled hypercalcemia (serum calcium-corrected greater than 12 mg/dL)

• Serious cardiac condition

• Any medical conditions that, in the investigator's opinion would impose excessive risk to the patient

• Patients with previous malignancies unless free of recurrence for at least 5 years except basal cell carcinoma of the skin or carcinoma-in-situ of the uterine cervix

• Treatment with antiretroviral therapy metabolized through CYP3A4