Safety Study of AP23573 in Patients With Advanced, Refractory or Recurrent Malignancies (8669-013)(COMPLETED)

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

Phase 1 trial to determine the safety, tolerability and maximum tolerated dose (MTD) of AP23573 in patients with refractory or recurrent malignancies, including myeloma and lymphoma.

The primary objectives of the study are to determine the safety, tolerability, and MTD of AP23573, when administered once daily for 5 days to be repeated every 2 weeks (two 2-week courses equals 1 cycle). The secondary objectives of the study are to characterize the pharmacokinetic profile of AP23573, to evaluate potential pharmacodynamic markers of AP23573, and to obtain preliminary information on the antineoplastic activity of AP23573.

Protocol Outline: This is a dose-escalation study. Patients receive AP23573 over 30 minutes by intravenous infusion once daily for 5 days to be repeated every 2 weeks. If tolerated, a total of at least 2 cycles will be administered (8-week treatment period). Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria:

(Patients must meet each of the following criteria to be eligible for participation in the study).

• 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 therapy.
• 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.

Exclusion Criteria:

(Patients meeting any of the following criteria are ineligible for participation in the study)

• 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 formulation.
• Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin).
• 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 studies.
• Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements.

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.