Phase II Sunitinib Prog Met AIPC

The following rationale can be made for a Phase II trial to evaluate sunitinib malate
(Sutent) for the therapy of progressive metastatic androgen-independent prostate cancer
(AIPC) following prior docetaxel chemotherapy. Since most patients with metastatic AIPC
following prior chemotherapy clinically progress rapidly, we believe that achieving a 30%
freedom from clinical progression (PFS) (not including PSA progression) at 12 weeks
represents biologically active therapy. Sunitinib malate (Sutent) represents a tolerable and
convenient form of therapy with the potential for improving outcomes in AIPC.

Inclusion Criteria:

- A patient will be eligible for inclusion in this study if he meets all of the
following criteria:

- Histologically confirmed, adenocarcinoma of the prostate

- Stage IV(metastatic) disease, documented on CT, MRI, or X-ray

- Progressive disease (PSA or clinical): PSA progression defined as baseline increase
followed by any serial increase after 2 weeks; clinical progression by symptomatic or
radiologic criteria.

- An elevated PSA level of for patients progressing by PSA criteria is required

- Currently on androgen ablation hormone therapy (an LHRH agonist or orchiectomy) with
testosterone level <50ng/dL)

- Has received 1 or 2 prior chemotherapy regimens (no more than 2). One prior regimen
must be docetaxel.

- Has an ECOG Performance Status (PS) 0-2

- Is greater than 18 years of age

- Meets protocol defined laboratory values

- Has adequate cardiac function in the opinion of the Investigator

- Has no uncontrolled arrhythmia or hypertension

- Resolution of all acute toxic effects of prior chemotherapy or surgical procedures to
NCI CTCAE Version 3.0 Grade less than 1, in the opinion of the Treating Physician

- If fertile, patient has agreed to use an acceptable method of birth control to prevent
pregnancy for the duration of the study and for a period of 2 months thereafter

- Has signed a Patient Informed Consent Form

- Has signed a Patient Authorization Form

Exclusion Criteria:

- A patient will be excluded from this study if he meets any of the following criteria:

- Has any disease other than that described in inclusion criterion #1

- Had prior treatment with Sutent

- Has not received prior docetaxel for the current disease

- Has received any prior radionuclide therapy

- Has received prior radiation to >50% of the bone marrow

- Is receiving concurrent immunotherapy

- Has a history of hypersensitivity to any of the components of Sutent: mannitol,
croscarmellose sodium, povidone (K-25) and magnesium stearate as inactive ingredients.
The orange gelatin capsule shells contain titanium dioxide, and red iron oxide. The
caramel gelatin capsule shells also contain yellow iron oxide and black iron oxide.
The printing ink contains shellac, propylene glycol, sodium hydroxide, povidone and
titanium dioxide.

- Has had significant bleeding in previous 4 weeks

- Has had any of the following within the prior 6 months: severe/unstable angina,
myocardial infarction, coronary/peripheral artery bypass graft, congestive heart
failure, cerebrovascular accident, transient ischemic attack, or pulmonary embolism

- Is receiving concurrent bisphosphonate therapy; long-standing bisphosphonate therapy
(initiated >8 weeks prior to registration) is acceptable. Bisphosphonates started
within the prior 8 weeks will not be allowed since this may affect other study
endpoints and render their interpretation difficult

- Has received treatment with radiation therapy, surgery, chemotherapy, ketoconazole,
corticosteroids, or an investigational agent within 4 weeks prior to registration, (6
weeks for radiation therapy, nitrosureas or Mitomycin C)

- Has uncontrolled arrhythmia or hypertension

- Has evidence of uncontrolled CNS involvement (previous radiation and off steroids is
acceptable)

- Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
the normal range with medication

- Has a serious uncontrolled intercurrent medical or psychiatric illness, including
serious infection

- Has a history of other malignancy within the last 5 years (except cured basal cell
carcinoma of skin), which could affect the diagnosis or assessment of any of the study
drugs

- Is unable to comply with requirements of study