Sipuleucel-T With or Without Tasquinimod in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

Study Overview
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Brief Summary
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This randomized phase II trial studies how well sipuleucel-T with or without tasquinimod works in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Tasquinimod may stop the growth of prostate cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether sipuleucel-T is more effective with or without tasquinimod in treating prostate cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine whether tasquinimod augments immune response to sipuleucel-T. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of the combination of sipuleucel-T and tasquinimod in patients with castration-resistant metastatic prostate cancer. II. To obtain preliminary evidence of the clinical benefit of the combination of sipuleucel-T and tasquinimod; to include changes in prostate specific antigen (PSA) over time, and duration of progression-free survival/overall survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive sipuleucel-T intravenously (IV) over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive tasquinimod orally (PO) once daily (QD) beginning on day -14 and sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients continue on tasquinimod treatment after day 42 until disease progression. After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Official Title
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A Phase II Randomized Open Label Study of Sipuleucel-T vs. Sipuleucel-T and Tasquinimod in Patients With Metastatic Castrate-Resistant Prostate Cancer (CRPC)

Conditions
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Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Biological: Sipuleucel-T
* Drug: Tasquinimod


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic asymptomatic or minimally symptomatic castration-resistant prostate cancer (CRPC) patients who are eligible for sipuleucel-T Disease progression by PSA criteria (PSA Working Group Consensus Criteria Eligibility) and/or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria Life expectancy >= 6 months Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Hemoglobin >= 100 g/L (>= 10 g/dL) Leukocytes >= 3,000/mm^3 Absolute neutrophil count >= 1,500/mm^3 Platelets >= 100,000/mm^3 Total bilirubin =< 1.5 x laboratory upper limit of normal Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x laboratory upper limit of normal Creatinine =< 1.5 x laboratory upper limit of normal or calculated creatinine clearance of >= 50 mL/min (please use institutional formula) Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 Urine protein < 1+; if >= 1+, 24 hour urine protein should be obtained and should be < 1000 mg Central nervous system (CNS): no recent history (within 6 month) of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases Ability to understand and the willingness to sign a written informed consent document Patient verbalizes the ability to swallow and retain oral medication Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Patients who have received systemic steroids within 4 weeks prior to starting study treatment Patients who have received prior immunotherapies History of therapy for an autoimmune disorder Patients receiving any other investigational agents Any medical condition that would preclude adequate evaluation of the safety and toxicity of the study combination Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Association class II, III, or IV), angina pectoris requiring nitrate therapy, recent myocardial infarction (less than the last 6 months), cardiac arrhythmia, history of cerebrovascular accident (CVA) within 6 months; no uncontrolled hypertension (defined as blood pressure of > 160/90 mmHg) on medication or, history of peripheral vascular disease Ongoing treatment with warfarin unless the international normalized ratio (INR) is well controlled and below 4 History of psychiatric illness or social situations that would limit compliance with study requirements History of pancreatitis Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible Systemic exposure to ketoconazole or other strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) isoenzyme inhibitors or inducers within 14 days prior to the start of study treatment; systemic exposure to aminodarone is not allowed within 1 year prior to the start of study treatment Ongoing treatment with sensitive cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of therapy Unwilling or unable to follow protocol requirements Any condition which in the investigator's opinion deems the patient an unsuitable candidate to receive study drug

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (sipuleucel-T)<br>Patients receive sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: Sipuleucel-T<br>* Given IV<br>* Other names: Provenge;|
| Experimental: Arm II (tasquinimod, sipuleucel-T)<br>Patients receive tasquinimod PO QD beginning on day -14 and sipuleucel-T IV over 60 minutes on day 4. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients continue on tasquinimod treatment after day 42 until disease progression. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: Sipuleucel-T<br>* Given IV<br>* Other names: Provenge;Drug: Tasquinimod<br>* Given PO<br>* Other names: TASQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Immune Response Assessed by IFN-g ELISPOT Specific for PA2024 |  | Baseline up to 50 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PSA Response | PSA doubling time, PSA slope | Baseline to up to 3 years | 
| Duration of PSA Response |  | Up to 3 years | 
| Frequency of Toxicities Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 | The frequency of participants with toxicities will be tabulated by grade across all dose levels and courses. | Up to 3 years | 
| Immune Response |  | Week 6 | 
| Immune Response |  | Week 10 | 
| Immune Response |  | Week 26 | 
| Immune Response |  | Week 50 | 
| Immune Response (Arm 2 Only) |  | Week 0 | 
| Objective Response Rates (Partial or Complete) |  | Up to 3 years | 
| Overall Survival |  | Up to 3 years | 
| Progression-free Survival |  | Up to 3 years | 
| Time to PSA Progression |  | Up to 3 years |