A Randomized Discontinuation Phase 2 Study of AZD0530 as a Metastasis Inhibitor in Castrate Resistant Prostate Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed prostate cancer with progressive disease;
progressive disease may be defined as either

- New clinical or radiographic metastases

- Rising PSA: PSA must be greater than 1.0 ng/mL with at least 2 consecutive rises
after completion of prior therapy; the PSA values documenting these rises should
be separated by no less than 10 days; the baseline PSA value may be taken from
the end of prior therapy

- Previous treatment with docetaxel for disease progression following hormonal therapy
(i.e., castrate-resistant disease) required

- Treatment in the adjuvant or neoadjuvant setting will NOT be grounds for
inclusion unless docetaxel has been used again in the setting of progressive
CRPC

- ECOG performance status 0-1

- ANC ≥ 1,500/mm³

- Hemoglobin > 9.0 g/dL

- Platelet count > 100,000/mm³

- Total bilirubin < 2.0 x institutional ULN

- AST/ALT < 5 x institutional ULN in the presence of bone/liver metastases

- Serum creatinine (Cr) within ULN

- Patients with Cr > ULN must have a Cr clearance of > 60 mL/min

- Testosterone 50 ng/mL or lower if a patient is receiving an LHRH agonist

- No testosterone testing is required for men who have undergone surgical
orchiectomy

- Fertile patients must agree to abstinence or some adequate form of contraception

- No patients with any condition (e.g., gastrointestinal tract disease resulting in an
inability to take oral medication or a requirement for IV alimentation, prior
surgical procedures affecting absorption, or active peptic ulcer disease) that
impairs the ability to swallow AZD0530 tablets

- No history of uncontrolled or unstable cardiac dysrhythmia

- No resting ECG with measurable QTc interval of > 480 msec at 2 or more time points
within a 24-hour period

- No evidence of interstitial lung disease (bilateral, diffuse, parenchymal lung
disease)

- A high-resolution CT of the chest will be required during screening

- No evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic
impairment) or current unstable or uncompensated respiratory or cardiac conditions
which makes it undesirable for the patient to participate in the study or which could
jeopardize compliance with the protocol

- No patients with a known immunodeficiency syndrome

- No patients with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to AZD0530

- No patients receiving any other investigational agents

- Previous AZD0530 exposure is allowed provided that the patient did not show
radiographic progression during treatment

- Patients receiving non-steroidal anti-androgens (e.g., flutamide) or other hormonal
treatment (such as ketoconazole, abiraterone, or TAK-700) must have stopped these
drugs at least 28 days prior to enrollment for flutamide or ketoconazole, or at least
42 days prior to enrollment for bicalutamide or nilutamide, and the patients must
have demonstrated progression of disease since the agents were suspended

- Patients should be at least 2 weeks away from previous chemotherapy, surgery, or
radiotherapy

- No unresolved toxicity from previous treatments that are CTCAE grade 2 from previous
anti-cancer therapy (except alopecia)

- Patients who are currently on zoledronic acid (Zometa) or other bisphosphonate
therapy are eligible provided that they have been on therapy at least 6 weeks prior
to participation

- Increases in bisphosphonate dosing will not be allowed (i.e., starting within 6
weeks or changing from every 3-month to every 1-month dosing)

- Use of specifically prohibited CYP3A4-active agents or substances are not permitted
during protocol treatment, and patients who must continue treatment with these agents
are not eligible

- Prohibited drugs should be discontinued 7 days prior to the administration of
the first dose of AZD0530 and for 7 days following discontinuation of AZD0530
(unless otherwise specified)

- No concurrent use of non-FDA approved medications