A Study of Sipuleucel-T With Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer

NCT ID: NCT01981122

Last Updated: 2018-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2017-06-30

Brief Summary

This is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide.

Detailed Description

This is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide. This study consists of 3 phases. The screening phase will begin at the completion of the informed consent process and continue through registration. The active phase will begin at registration and continue through the post-treatment visit (30 to 37 days following the last study treatment). The long term follow-up (LTFU) phase will begin after the post-treatment visit and will continue until the subject's death or until Dendreon terminates the study.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Concurrent Arm

Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first.

Group Type: EXPERIMENTAL

sipuleucel-T

Intervention Type: BIOLOGICAL

Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

enzalutamide

Intervention Type: DRUG

Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.

Sequential Arm

Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first.

Group Type: EXPERIMENTAL

sipuleucel-T

Intervention Type: BIOLOGICAL

Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

enzalutamide

Intervention Type: DRUG

Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.

Interventions

sipuleucel-T

Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

Intervention Type: BIOLOGICAL

enzalutamide

Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.

Intervention Type: DRUG

Other Intervention Names

PROVENGE(R); APC8015; Xtandi

Eligibility Criteria

Inclusion Criteria

• Written informed consent provided prior to the initiation of study procedures.
• Age ≥ 18 years.
• Histologically documented adenocarcinoma prostate cancer confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen.
• Metastatic disease as evidenced by bone metastasis or lymph node metastasis.
• Castrate-resistant prostate cancer as demonstrated by one of the following:

• Prostate specific antigen progression.
• Progression of measurable disease.
• Progression of non-measurable disease by soft tissue disease or bone disease.
• Castration levels of testosterone (≤ 50 ng/dL) achieved via medical or surgical castration.
• Serum PSA (Prostate specific antigen) ≥ 2.0 ng/mL.
• Screening ECOG (The Eastern Cooperative Oncology Group )performance status ≤ 1
• Adequate screening hematologic, renal, and liver function as evidenced by laboratory test results obtained ≤ 28 days prior to registration.
• Negative serology test for human immunodeficiency virus 1 and 2.
• Resides within driving distance (round trip within 1 day) of the clinical trial site for the duration of the active phase.

Exclusion Criteria

• The presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites.
• Spinal cord compression, imminent long bone fracture, or any other condition that is likely to require radiation therapy and/or steroids for pain control during the active phase.
• History of stage 3 or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the subject must be disease free at the time of registration. Subjects with a history of stage 1 or 2 cancer must have been adequately treated and been disease free for ≥ 3 years at the time of registration.
• History of seizures or of predisposing factors for seizures.
• Child-Pugh Class C hepatic insufficiency.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T, GM-CSF or granulocyte colony stimulating factor (G-CSF).
• Previous treatment with sipuleucel-T or enrollment in a sipuleucel-T trial, regardless of whether the subject received sipuleucel-T or control.
• Previous treatment with enzalutamide.
• Previous treatment with abiraterone acetate.
• Previous treatment with ipilimumab.
• Previous treatment with ketoconazole other than topical use or for treatment of infections (e.g., oral thrush); most recent use must have been ≥ 7 days prior to registration.
• Previous treatment with any immunotherapy or investigational vaccine.
• A requirement for ongoing systemic immunosuppressive therapy. Use of inhaled, intranasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed.
• Previous treatment with chemotherapy for mCRPC, or chemotherapy for any reason ≤ 2 years prior to registration.
• Use of concomitant medications that may lower the seizure threshold or the use of antiseizure medications ≤ 1 year prior to registration.
• Received GM-CSF or G-CSF ≤ 90 days prior to registration.
• Ongoing non-steroidal antiandrogen withdrawal response.
• Any of the following medications or interventions ≤ 28 days prior to registration:

• Radiation therapy, either via external beam or brachytherapy.
• Any systemic steroid. Use of inhaled, intra-nasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed.
• Any systemic therapy for prostate cancer, except for ADT (Androgen deprivation therapy).
• Any investigational product for prostate cancer.
• Major surgery requiring general anesthesia, with the exception of placement of central venous catheters.
• Inducers and inhibitors of cytochrome P450 (CYP) enzyme CYP2C8 (gemfibrozil and rifampin).
• Medications that are metabolized by CYP3A4, CYP2C9, or CYP2C19 that have a narrow therapeutic index.
• Inducers of CYP3A4 (including but not limited to phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital).
• A requirement for treatment with opioid analgesics for cancer-related pain ≤ 21 days prior to registration.
• An active infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5˚ F or 38.1˚ C) ≤ 1 week prior to registration.
• Any medical intervention, any other condition, or any other circumstance which could compromise adherence with study requirements or otherwise compromise the study's objectives.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Dendreon

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruce Brown, MD

Role: STUDY_DIRECTOR

Dendreon Pharmaceuticals, LLC

Locations

Urological Associates of Southern Arizona, P.C.

Tucson, Arizona, United States

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Yale University School of Medicine

New Haven, Connecticut, United States

H. Lee Moffitt Cancer and Research Center

Tampa, Florida, United States

Uro Partners/ RMD Clinical Research

Melrose Park, Illinois, United States

Fort Wayne Medical Oncology and Hematology, Lutheran Hospital, Parkview Regional Medical Center

Fort Wayne, Indiana, United States

Johns Hopkins Medicine - Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

GU Research Network

Omaha, Nebraska, United States

North Shore Hematology/Oncology Associates, P.C.

East Setauket, New York, United States

Associated Medical Professionals of New York, PLLC

Syracuse, New York, United States

Raleigh Hematology Oncology Associates, D.B.A. Cancer Centers of North Carolina

Raleigh, North Carolina, United States

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Urology Associates, PC

Nashville, Tennessee, United States

Urology of Virginia

Virginia Beach, Virginia, United States

Virginia Mason Medical Center, Virginia Mason Hospital

Seattle, Washington, United States

Northwest Medical Specialties, Rainier Physicians

Tacoma, Washington, United States

Countries

United States

References

Antonarakis ES, Subudhi SK, Pieczonka CM, Karsh LI, Quinn DI, Hafron JM, Wilfehrt HM, Harmon M, Sheikh NA, Shore ND, Petrylak DP. Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials. Clin Cancer Res. 2023 Jul 5;29(13):2426-2434. doi: 10.1158/1078-0432.CCR-22-3832.

Reference Type: DERIVED

PMID: 37058234 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

P12-2

Identifier Type: -

Identifier Source: org_study_id