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

Phase 2

Completed

• Conditions: Metastatic Prostate Cancer
• Interventions: Biological: sipuleucel-T; Drug: enzalutamide

• Registration Number: NCT01981122
• Lead Sponsor: Dendreon

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.

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-10-29
• Study First Submitted QC: 2013-11-05
• Study First Posted: 2013-11-11
• Primary Completion: 2017-06-30
• Study Completion: 2017-06-30
• Results First Submitted: 2018-07-24
• Results First Submitted QC: 2018-08-24
• Status Verified: 2018-09
• Results First Posted: 2018-09-25
• Last Update Submitted: 2018-09-25
• Last Update Posted: 2018-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 52

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Concurrent Arm	enzalutamide	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.
Concurrent Arm	sipuleucel-T	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.
Sequential Arm	sipuleucel-T	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.
Sequential Arm	enzalutamide	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.

Primary Outcome Measures

Name	Time	Method
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI).	Each patient was followed for up to 52 weeks after the first dose of sipuleucel-T. Immune sample draws during the treatment period (Week 0 through Week 4) were to be performed at the patient's pre-leukapheresis visits (Pre-Leuk 2 and Pre-Leuk 3).	PA2024-specific T cell proliferation responses over time will be compared between the concurrent arm and sequential arm using a repeated measurement mixed model analysis. The unit of analysis for the T cell proliferation data is the stimulation index, defined as the median 3H uptake of 3 wells exposed to antigen divided by the median 3H thymidine uptake of 3 wells exposed to media. The stimulation index will be log-transformed prior to analysis.

Trial Locations

Locations (19)

Urology of Virginia; 🇺🇸 Virginia Beach, Virginia, United States

Northwest Medical Specialties, Rainier Physicians; 🇺🇸 Tacoma, Washington, United States

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Fort Wayne Medical Oncology and Hematology, Lutheran Hospital, Parkview Regional Medical Center; 🇺🇸 Fort Wayne, Indiana, United States

Uro Partners/ RMD Clinical Research; 🇺🇸 Melrose Park, Illinois, United States

North Shore Hematology/Oncology Associates, P.C.; 🇺🇸 East Setauket, New York, United States

Johns Hopkins Medicine - Sidney Kimmel Comprehensive Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Cleveland Clinic - Taussig Cancer Institute; 🇺🇸 Cleveland, Ohio, United States

GU Research Network; 🇺🇸 Omaha, Nebraska, United States

The Urology Center of Colorado; 🇺🇸 Denver, Colorado, United States

Urology Associates, PC; 🇺🇸 Nashville, Tennessee, United States

Virginia Mason Medical Center, Virginia Mason Hospital; 🇺🇸 Seattle, Washington, United States

Raleigh Hematology Oncology Associates, D.B.A. Cancer Centers of North Carolina; 🇺🇸 Raleigh, North Carolina, United States

H. Lee Moffitt Cancer and Research Center; 🇺🇸 Tampa, Florida, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Associated Medical Professionals of New York, PLLC; 🇺🇸 Syracuse, New York, United States

Urological Associates of Southern Arizona, P.C.; 🇺🇸 Tucson, Arizona, United States

Carolina Urologic Research Center; 🇺🇸 Myrtle Beach, South Carolina, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States