A Phase I Sequential Ascending Dose Trial of AP23573 in Patients With Progressive or Recurrent Malignant Glioma

Inclusion Criteria

Inclusion Criteria (Patients must meet each of the following criteria to be eligible for
participation in the trial):

- Male or female patients ≥ 18 years of age

- Patients must have a radiographically suspected progressive or recurrent primary
malignant glioma (glioblastoma multiforme or gliosarcoma) and must have failed
standard therapy. Patients may not have received any systemic therapy for the
treatment of this recurrence or relapse

- Patients must be candidates for surgical resection or open biopsy of the tumor

- Patients who have had previous surgical resection(s) are eligible

- Patients must have had minimum prior therapy of radiotherapy and documented
progression of disease thereafter

- Patients must have had a tissue proven malignant glioma

- A minimum interval of at least four weeks prior to the first dose of AP23573 must
have elapsed for all patients enrolling after either prior surgery or completion of
prior external beam radiotherapy for initial primary diagnosis

- A minimum interval of four weeks prior to the first dose of AP23573 must have elapsed
since receipt of any investigational therapy or any other chemotherapy

- Patients in the EIAC cohorts must be presently receiving a stable dose of EIAC (e.g.,
dilantin, phenytoin, etc.) for at least two weeks prior to the first dose of AP23573

- For patients on corticosteroids, the dose must be stable for at least one week prior
to the first dose of AP23573

- Patients must be neurologically stable for at least two weeks prior to the first dose
of AP23573

- Patients must have an ECOG performance status of 0 or 1

- Patients must either not be of childbearing potential or have agreed to use a
medically effective method of contraception

- Patients must have adequate hematologic, renal and liver function as specified in the
protocol

- Patients must be able to understand and give written informed consent

Exclusion Criteria (Patients meeting any of the following criteria are ineligible for
participation in the trial):

- Women who are pregnant or lactating

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

- Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin,
erythromycin, azithromycin)

- Patients with significant cardiovascular disease, as specified in the protocol

- Patients with known HIV infection

- Patients with any active infection requiring prescribed intervention

- Patients receiving immunosuppressive agents other than prescribed corticosteroids

- Patients who have had prior therapy with rapamycin, any rapamycin analog or
tacrolimus

- Patients with inadequate recovery from any prior surgical procedure or patients
having undergone any major surgical procedure within two weeks prior to the first
dose of AP23573

- Patients with 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 evaluation of the safety of the study drug

- Patients with a psychiatric disorder or altered mental status that would preclude
understanding of the informed consent process and/or completion of the necessary
studies

- Patients with another primary malignancy within the past three years (except for
non-melanoma skin cancers and cervical carcinomas in situ)

- Patients with the inability, in the opinion of the Investigator, to comply with the
protocol requirements

- Patients are not permitted any chemotherapeutic agents or other antineoplastic agents
either during or within four weeks prior to the first dose of AP23573. Additional
excluded drugs and treatments are specified in the protocol