A Phase II Study of AP23573, An mTOR Inhibitor, in Patients With Advanced Sarcoma

Inclusion Criteria:

- Patients ≥15 years of age with metastatic and/or unresectable sarcomas of the
following histological subgroups: Bone sarcomas, such as osteosarcoma and Ewings
sarcoma; Leiomyosarcoma; Liposarcomas; Any other soft tissue sarcoma except
gastrointestinal stromal tumors (GIST). Patients with well-differentiated
liposarcoma or desmoid tumors must have demonstrated progressive disease within the
previous 6 months

- 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 computerized tomography (CT) scan (or otherwise at least twice the
reconstruction interval for CT or magnetic resonance imaging [MRI] scans)

- Eastern Cooperative Oncology Group (ECOG) performance status ≤1

- Minimum life expectancy of 3 months

- Adequate renal and hepatic function, as specified in the protocol

- Adequate bone marrow function, as specified in the protocol

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

- Male and female patients who are not surgically sterile or postmenopausal must agree
to use reliable methods of birth control for the duration of the study until 30 days
after the last dose of study drug

- Able to understand and give written informed consent

Exclusion Criteria:

- Women who are pregnant or lactating

- Presence of brain metastases

- Prior therapy with rapamycin, rapamycin analogues or tacrolimus

- Prior anticancer treatment (chemotherapy, radiotherapy, hormonal, immunotherapy,
biological response modifiers, signal transduction inhibitors, etc) within 4 weeks
prior to the first dose of ridaforolimus

- 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 human immunodeficiency virus (HIV) infection

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

- Concurrent treatment with immunosuppressive agents other than prescribed
corticosteroids at stable doses for 2 weeks prior to first planned dose of study drug

- Inadequate recovery from any prior surgical procedure or having undergone any major
surgical procedure within 2 weeks prior to the first dose of ridaforolimus

- 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