PTC299 and Hormonal Agent for Treatment of Metastatic Breast Cancer

The study will be conducted in 2 stages. In Stage 1 of the study, successive groups of 3 to 6 patients will receive progressively higher PTC299 dose levels; in this stage, treatment will be given in repeated 6-week cycles consisting of 4 weeks of oral PTC299 twice per day followed by a 2-week, no-drug period. During Stage 2, study candidates must be women with natural or induced suppression of ovarian function to post-menopausal levels who are receiving or are candidates for hormonal therapy. These subjects will receive continuous administration of PTC299, 100 mg/dose BID, in repeated 6-week cycles in combination with continuous administration of one of 3 hormonal agents. All planned PTC299 dose levels in all stages are expected to achieve circulating blood levels of PTC299 known to be active in animal models of human cancer. Treatment for each patient can continue as long as the therapy appears to be safely offering tumor control to that patient. Up to 36 evaluable patients will be accrued across both stages.

Major Eligibility Criteria:

• Female sex.
• Age ≥18 years.
• Body weight 40-100 kg.
• ECOG performance status of 0 or 1.
• Histologically or cytologically confirmed adenocarcinoma of the breast.
• Presence of metastatic disease not amenable to surgery, radiation therapy, or chemoradiotherapy with curative intent.
• No active second metastatic malignancy other than breast cancer.
• No unstable brain or leptomeningeal disease.
• Discontinuation of other therapies (except for anastrozole, letrozole, or exemestane) for the treatment of breast cancer and resolution of any acute toxic effects of prior therapies.
• Adequate bone marrow, liver, and kidney function.
• No uncontrolled hypertension, major bleeding, HIV infection or recent acute cardiovascular event.
• If sexually active and not postmenopausal or surgically sterile, willingness to abstain from sexual intercourse or employ an effective barrier method of contraception during the study drug administration and follow-up periods.
• No pregnancy or breast-feeding.
• Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• Willingness to provide informed consent. In addition to the criteria noted above, Stage 2 subjects must also have natural or induced suppression of ovarian function to post-menopausal levels and be receiving or be a candidate for hormonal therapy.