A Phase II Study of the Efficacy and Safety of AP23573 in Patients With Taxane-Resistant Androgen-Independent Prostate Cancer (AIPC)
- Male patients aged ≥ 18 years with histologically documented adenocarcinoma of the
- Clinically refractory to hormone therapy (orchiectomy or luteinizing
hormone-releasing hormone agonist/antagonist).
- Presence of metastatic prostate cancer that fulfills at least one evaluation category
as listed: * Measurable Disease: Lesion(s) that can be accurately measured in at
least one dimension with the longest diameter ≥ 20 mm using conventional techniques
or ≥ 10 mm with spiral CT scan (or otherwise at least twice the reconstruction
interval for CT or MRI scans). *Non-measurable disease: Lesions noted on imaging
studies (including metastatic bone lesions on bone scan) or other non-measurable
lesions as defined by the modified RECIST criteria. *Progressive disease following a
cytotoxic chemotherapy regimen for prostate cancer.
- Previous treatment with at least one taxane-containing chemotherapy regimen.
Patients may have received treatment with not more than 3 additional regimens of
cytotoxic chemotherapy prior to study entry.
- Orchiectomy, or castrate levels of testosterone maintained by LHRH agonist/antagonist
< 50 ng/mL.
- Predicted life expectancy > 12 weeks.
- ECOG PS ≤ 2.
- Adequate renal and hepatic function, defined as: *Total serum bilirubin ≤ 1.5 x ULN
for the institution; *AST and/or ALT ≤ 3 x ULN for the institution (≤ 5 x ULN if
liver metastases are present); *Serum albumin ≥ 2.5 g/dL; *Serum creatinine ≤1.5 x
ULN for the institution (or a calculated creatinine clearance ≥ 50 mL/min/1.73m2)
- 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.
- Male patients who are not surgically sterile must agree to use reliable methods of
birth control for the duration of the study until 30 days after the last dose of
- Able to understand and give written informed consent.
- Presence of active or progressive brain metastases.
- Prior therapy with rapamycin, rapamycin analogues or tacrolimus.
- Prior non-hormonal anticancer treatment (chemotherapy, radiotherapy, immunotherapy,
biological response modifiers, signal transduction inhibitors, etc.) within 4 weeks
prior to the first dose of AP23573
- Ongoing toxicity associated with prior anticancer therapy (except peripheral
neuropathy of ≤ grade 1 by NCI toxicity criteria).
- Another primary malignancy within the past three years (except for non-melanoma skin
- 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,
- 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
- Concurrent treatment with immunosuppressive agents other than prescribed
corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study
- Inadequate recovery from any prior surgical procedure or having undergone any major
surgical procedure within 2 weeks prior to the first dose of AP23573.
- 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.