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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer; Hormone-Resistant Prostate Cancer
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Sipuleucel-T; Drug: Tasquinimod

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (sipuleucel-T); 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; Correlative studies; Biological: Sipuleucel-T; Given IV; Other Names: APC8015; Provenge; APC8015 Vaccine; PA2024 (PAP/GM-CSF)-Loaded Dendritic Cell Vaccine
Experimental: Arm II (tasquinimod, sipuleucel-T); 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; Correlative studies; Biological: Sipuleucel-T; Given IV; Other Names: APC8015; Provenge; APC8015 Vaccine; PA2024 (PAP/GM-CSF)-Loaded Dendritic Cell Vaccine; Drug: Tasquinimod; Given PO; Other Names: ABR-215050; TASQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
Overall Survival		Up to 3 years
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
Progression-free Survival		Up to 3 years
Time to PSA Progression		Up to 3 years

Other Outcome Measures

Outcome Measure	Time Frame
Effects of Tasquinimod on the Inhibition of Immune Cells	Up to week 50

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: Active Biotech AB

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: June 9, 2014
• First Submitted That Met QC Criteria: June 9, 2014
• First Posted (Estimate): June 10, 2014

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Carcinoma; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: I 250813 (Other Identifier: Roswell Park Cancer Institute); NCI-2014-01184 (Registry Identifier: CTRP (Clinical Trial Reporting Program))