Sunitinib Plus Prednisone In Patients With Metastatic Castration-Resistant Prostate Cancer After Failure Of Docetaxel Chemotherapy

Study Overview
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Brief Summary
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This study will compare the safety and efficacy of sunitinib in combination with prednisone versus placebo and prednisone in patients that have metastatic castration-resistant prostate cancer that has progressed after treatment with a docetaxel-containing chemotherapy regimen. This is a second-line study.

Official Title
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A Multicenter, Randomized, Double-Blind, Phase 3 Study Of Sunitinib Plus Prednisone Versus Prednisone In Patients With Progressive Metastatic Castration-Resistant Prostate Cancer After Failure Of A Docetaxel-Based Chemotherapy Regimen

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Prednisone
* Drug: sunitinib
* Drug: Placebo
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate. Progressive, metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy (resistant or intolerant). Progressive disease based on PSA progression, RECIST, or positive bone scan. ECOG 0 or 1. Exclusion Criteria: Prior treatment with sunitinib and/or more than 1 prior chemotherapy regimen in the metastatic disease setting. Chemotherapy within 3 weeks. Impending complications from bone metastases. Ongoing urinary obstruction. Cardiac dysfunction, QTc >470 msec. CNS involvement.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Treatment Arm A - sunitinib + prednisone | Drug: Prednisone<br>* 5 mg BID, oral<br>* Other names: Deltasone;Drug: sunitinib<br>* 37.5 mg/day, oral, administered on a continuous daily dosing regimen<br>* Other names: Sutent, SU011248;|
| Placebo Comparator: B<br>Treatment Arm B - placebo + prednisone | Drug: Placebo<br>* 37.5 mg/day, oral, administered on a continuous daily dosing regimen<br>Drug: Prednisone<br>* 5 mg BID, oral<br>* Other names: Deltasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is the duration from randomization to death. For participants who were alive, overall survival was censored at the last contact. OS (in months) calculated as (date of death minus [-] date of randomization plus [+] 1) divided (/) 30.4. | Baseline up to 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is the period from randomization until disease progression or death on study. PFS is censored on the date of last tumor assessment documenting absence of progressive disease. PFS (weeks) calculated as (first event date - randomization date + 1)/7.02 | Baseline, every 8 weeks up to 123 weeks | 
| Percent of Participants With Objective Response (OR) | OR defined as the percent (%) of participants with confirmed Complete Response (CR) (disappearance of all target lesions) or Partial Response (PR) (>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to Response Evaluation Criteria in Solid Tumors (RECIST), relative to the full analysis population. Confirmed responses were those that persist on repeat imagining study >= 4 weeks after initial documentation of response. | Baseline, every 8 weeks up to 123 weeks | 
| Duration of Response (DR) | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cause - the date of the first CR or PR that was subsequently confirmed plus 1 divided by 7.02. DR calculated for the subgroup of participants with a confirmed objective tumor response | Baseline, every 8 weeks up to 123 weeks | 
| Change From Baseline in Pain Severity | Pain severity recorded on a numerical scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). Higher scores indicated greater level of pain. The pain score for each cycle averaged for the 7 days. | Day 1 through Day 7 every 28 days (every cycle) up to 29 months | 
| Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) | FACT-P is a validated, self-administered instrument used to assess health-related quality of life and prostate cancer-specific symptoms. Scores ranged from 0 (not at all) to 4 (very much). It is 27-item FACT-General and 12 items for the prostate cancer specific concerns. The 27 items in FACT-G are grouped into 4 domains: physical well-being, social/family well-being, emotional well-being and functional well-being. The 12 prostate cancer symptoms items focus on pain (3 items), urination problems (3 items), sexual functions (2 items), weight loss, appetite, overall comfort, and bowel movement. | Baseline, every 4 weeks up to 123 weeks | 
| Change From Baseline in Euro Quality of Life (EQ-5D)- Health State Profile Utility Score | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Overall scores range from 0 to 1, with lower scores representing a higher level of dysfunction. | Baseline, every 4 weeks up to 123 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Docetaxel-refractory mCRPC, Second-line treatment with sunitinib and prednisone