A Phase II Study of AP23573, an mTOR Inhibitor, in Female Adult Patients With Recurrent or Persistent Endometrial Cancer

Inclusion Criteria:

- ≥18 years of age with histologically confirmed endometrial cancer

- Documented progression of endometrial cancer (e.g., within the last 3 months)

- If of childbearing potential, must agree to use approved barrier methods of
contraception (non hormonal methods)

- Presence of at least one measurable lesion that can be accurately measured in at
least one dimension with longest diameter ≥20 mm using conventional techniques or ≥10
mm with spiral computed tomography (CT) scan (or otherwise at least twice the
reconstruction interval for CT or magnetic resonance imaging [MRI] scans). Previously
irradiated lesions may be considered to be measurable provided: *there has been
documented progression of the lesion(s) since completion of radiotherapy; and *the
criteria for measurability as outlined above are met.

- ECOG performance status ≤ 2

- Minimum life expectancy of 3 months

- Adequate renal and hepatic function, defined as:

- Total serum bilirubin ≤ 1.5 x ULN for the institution;

- AST and/or ALT ≤ 2 x ULN for the institution;

- Alkaline phosphatase < 1.5 x ULN for the institution (if > 1.5 x ULN, then
alkaline phosphatase liver fraction must be < 1.5 ULN);

- Serum albumin ≥ 2.5 g/dL;

- Serum creatinine ≤ 1.5 x ULN for the institution.

- Adequate bone marrow function, defined as:

- ANC ≥ 1.5 x 10^9/L;

- Platelet count ≥ 100 x 10^9/L.

- Serum cholesterol <350 mg/dL and triglycerides < 400 mg/dL

- Able to understand and give written informed consent

Exclusion Criteria:

- Women who are pregnant or lactating

- Presence of brain metastases

- More than 2 prior regimens of cytotoxic chemotherapy or enzyme inhibitor therapy

- Prior therapy with rapamycin, rapamycin analogues or tacrolimus; or known sensitivity
to these agents

- Anticancer treatment (chemotherapy, radiotherapy, immunotherapy, biological response
modifiers, signal transduction inhibitors, etc.) within 4 weeks prior to the first
dose of AP23573. The interval may be ≥ 2 weeks for hormonal therapy or signal
transduction inhibitors with a half-life known to be <24 hours and must be ≥ 6 weeks
for nitrosourea or mitomycin.

- Ongoing toxicity associated with prior anticancer therapy (except peripheral
neuropathy of ≤ Grade 1 by National Cancer Institute [NCI] toxicity criteria)

- Another primary malignancy within the past three years (except for non-melanoma skin
cancer and cervical carcinoma in situ)

- Known or suspected hypersensitivity to drugs formulated with polysorbate 80 (Tween)
or any other excipient contained in the study drug

- Known Grade 3 or 4 hypersensitivity to macrolide antibiotics (e.g., clarithromycin,
erythromycin, azithromycin)

- Significant uncontrolled cardiovascular disease

- Active infection requiring systemic therapy

- Known HIV infection

- Treatment with any investigational agent within 4 weeks prior to the first dose of
AP23573

- Concurrent treatment with immunosuppressive agents other than prescribed
corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study
drug. Nasal, ophthalmic, and topical glucocorticoid preparations are allowed as
well as low dose maintenance steroid therapy for other conditions. Physiologic
hormone replacement therapy (e.g., thyroid supplementation for thyroid deficiency or
oral replacement glucocorticoid therapy for adrenal insufficiency) is allowed.

- Inadequate recovery from any prior surgical procedure or having undergone any major
surgical procedure within 2 weeks prior to the first dose of AP23573. Patients who
have recovered from placement of a central venous access port within 2 weeks of Cycle
1, Day 1 will be considered eligible.

- Presence of any other life-threatening illness or organ system dysfunction which, in
the opinion of the Investigator, would either compromise the patient's safety or
interfere with evaluating the safety of the study drug