A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Daily x 5 Administration of AP23573, an mTOR Inhibitor, in Patients With Refractory or Advanced Malignancies
(Patients must meet each of the following criteria to be eligible for participation in the
- Male or female patients, ≥ 18 years of age.
- Patients with a documented measurable or evaluable malignancy, including myeloma or
lymphoma, that is recurrent, advanced, or metastatic.
- Patients with disease that is currently refractory to, or not amenable to, standard
- Patients with disease that is currently not amenable to surgical intervention.
- Patients with Karnofsky performance status of ≥ 70% (ECOG performance status of 0 or
1) and an anticipated life expectancy of ≥ 3 months.
- Patients either not of childbearing potential, or agreeing to use a medically
effective method of contraception.
- Patients with the ability to understand and give written informed consent.
(Patients meeting any of the following criteria are ineligible for participation in the
- Women who are pregnant or lactating.
- Patients with primary CNS malignancies. Patients with leukemia, any form.
- Patients with certain hematologic abnormalities.
- Patients with certain serum chemistry abnormalities at baseline.
- Patients with known or suspected hypersensitivity to either drugs formulated with
polysorbate 80 (Tween 80) or any other excipient contained in the test drug
- Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin,
- Patients with significant cardiovascular disease.
- Patients with active CNS metastases (or leptomeningeal disease) not controlled by
prior surgery or radiotherapy. Note: Patients with treated brain metastases will
be eligible if they are on a stable dose of corticosteroids or are without change in
brain disease status for at least 4 weeks following related therapy (e.g., whole
brain radiation, surgery).
- Patients with known HIV infection.
- Patients with any active infection.
- Patients with inadequate recovery from any prior surgical procedure, or patients
having undergone any major surgical procedure within 2 weeks prior to study entry.
Note: Patients having undergone recent placement of a central venous access port
will be considered eligible for enrollment if they have recovered.
- Patients who have 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 test 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
- Patients with the inability, in the opinion of the Investigator, to comply with the
Drugs and Other Treatments to be Excluded (Either during or within 4 weeks prior to study
entry, unless otherwise noted)
- Chemotherapeutic agents (standard or experimental).
- Other antineoplastic agents.
- Immunotherapy (including vaccines) or biological response modifier therapy.
- Systemic hormonal therapy.
- Herbal preparations or related OTC preparations containing herbal ingredients (e.g.,
St John's Wort) during or within 2 weeks prior to study entry.
- Any prior therapy with rapamycin, CCI-779, or any other rapamycin analog.
- Any other experimental therapy during the course of the study.
- Radiotherapy for the primary malignancy or metastases.