Phase II Sunitinib Prog Met AIPC

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to find out what effects (good and bad) Sutent has on you and your prostate cancer.

Detailed Description
-----------------
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.

Official Title
-----------------
Phase II Trial of Sunitinib Malate for the Therapy of Progressive Metastatic Androgen Independent Prostate Cancer (AIPC) Following Docetaxel-based Chemotherapy

Conditions
-----------------
Metastatic Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Sunitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib Malate<br>Sunitinib Malate (Sutent) (50 mg/day on Days 1-28 of 42-day cycles) | Drug: Sunitinib<br>* 50 mg/day orally each of Days 1-28 of each 6 week cycle<br>* Other names: Sutent;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression-free Survival (PFS) Time at 1-year. | PFS is measured from the date of registration to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overal Survival (OS) Rate at 1-year. | OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. | 12 months | 
| Prostate Specific Antigen (PSA) Response | Percentage of participants whose PSA value declined to 50% when compared to the value at the baseline. | Baseline and up to 12 months | 
| Change of PSA Doubling Time | Difference of PSA doubling time between baseline and end of the treatment. | Baseline and up to 12 months | 
| Objective Response Rate (ORR) | ORR = Complete Response (CR) + Partial response (PR). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. | 12 months | 
| Percentage of Participants With Decrease in Present Pain Intensity (PPI) From Baseline. | Pain score decreased >=2 points from baseline. The PPI scale has the following descriptors: 0=no pain, 1=mild pain, 2=discomforting pain, 3=distressing pain, 4=horrible pain, and 5=excruciating pain. The patient will be asked to self-assess and record their PPI in the study diary. Upon diary review, the study nurse will utilize the PPI daily scores to calculate the week's average. The weekly PPI score during the study is the average of the daily PPI scores, based on a minimum of 3 daily PPI assessments during a week's period. | Baseline and up to 12 months |