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

Metastatic Prostate Cancer Clinical Trial

Official title:

A Randomized, Open-label, Phase 2 Study of Sipuleucel-T With Concurrent Versus Sequential Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01981122
• Other study ID #: P12-2
• Status: Completed
• Phase: Phase 2
• Start date: September 2013
• Est. completion date: June 30, 2017

Study information

• Verified date: September 2018
• Source: Dendreon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 30, 2017
• Est. primary completion date: June 30, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• 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).

Drug:
• 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.

Locations

Country	Name	City	State
United States	Johns Hopkins Medicine - Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Cleveland Clinic - Taussig Cancer Institute	Cleveland	Ohio
United States	The Urology Center of Colorado	Denver	Colorado
United States	North Shore Hematology/Oncology Associates, P.C.	East Setauket	New York
United States	Fort Wayne Medical Oncology and Hematology, Lutheran Hospital, Parkview Regional Medical Center	Fort Wayne	Indiana
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Uro Partners/ RMD Clinical Research	Melrose Park	Illinois
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Urology Associates, PC	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	GU Research Network	Omaha	Nebraska
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Raleigh Hematology Oncology Associates, D.B.A. Cancer Centers of North Carolina	Raleigh	North Carolina
United States	Virginia Mason Medical Center, Virginia Mason Hospital	Seattle	Washington
United States	Associated Medical Professionals of New York, PLLC	Syracuse	New York
United States	Northwest Medical Specialties, Rainier Physicians	Tacoma	Washington
United States	H. Lee Moffitt Cancer and Research Center	Tampa	Florida
United States	Urological Associates of Southern Arizona, P.C.	Tucson	Arizona
United States	Urology of Virginia	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Dendreon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI).	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.	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).