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

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.

• Laboratory Biomarker Analysis (Other): Correlative studies
• Sipuleucel-T (Biological), also known as APC8015, APC8015 Vaccine, PA2024 (PAP/GM-CSF)-Loaded Dendritic Cell Vaccine, Provenge: Given IV
• Tasquinimod (Drug), also known as ABR-215050, TASQ: Given PO

Primary outcomes

• Change in Immune Response Assessed by IFN-g ELISPOT Specific for PA2024 [Baseline up to 50 weeks]

Secondary outcomes

• Change in PSA Response [Baseline to up to 3 years]: PSA doubling time, PSA slope
• 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 [Up to 3 years]: The frequency of participants with toxicities will be tabulated by grade across all dose levels and courses.
• 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]

Other outcomes

• Effects of Tasquinimod on the Inhibition of Immune Cells [Up to week 50]

Sex: Male, ages: 18 Years to any

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

Participant flow

Outcome results

• Change in Immune Response Assessed by IFN-g ELISPOT Specific for PA2024 (Primary)
• Change in PSA Response (Secondary)
• Duration of PSA Response (Secondary)
• Frequency of Toxicities Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (Secondary), Number, participants: Arm I (Sipuleucel-T) ; Arm II (Tasquinimod, Sipuleucel-T) 1
• Immune Response (Secondary)
• Immune Response (Secondary)
• Immune Response (Secondary)
• Immune Response (Secondary)
• Immune Response (Arm 2 Only) (Secondary)
• Objective Response Rates (Partial or Complete) (Secondary)
• Overall Survival (Secondary)
• Progression-free Survival (Secondary)
• Time to PSA Progression (Secondary)
• Effects of Tasquinimod on the Inhibition of Immune Cells (Other pre specified)

Adverse events

Serious adverse events by term

Other adverse events by term

Limitations and caveats: Due to the study's early closure, as a result of lack of funding, target accrual was not reached and no statistical inference of the primary and secondary aims were carried forth.

• Saby George, Principal investigator, Roswell Park Cancer Institute