Clinical trial NCT01981122: A Study of Sipuleucel-T With Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Prostate Cancer
Lead sponsor: Dendreon
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 52
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI).
timeFrame: 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).
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, P.C.
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer and Research Center
state: Florida
city: Melrose Park
country: United States
facility: Uro Partners/ RMD Clinical Research
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Lutheran Hospital, Parkview Regional Medical Center
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Medicine - Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Omaha
country: United States
facility: GU Research Network
state: Nebraska
city: East Setauket
country: United States
facility: North Shore Hematology/Oncology Associates, P.C.
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of New York, PLLC
state: New York
city: Raleigh
country: United States
facility: Raleigh Hematology Oncology Associates, D.B.A. Cancer Centers of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Institute
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, PC
state: Tennessee
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center, Virginia Mason Hospital
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties, Rainier Physicians
state: Washington
Study officials:
affiliation: Dendreon Pharmaceuticals, LLC
name: Bruce Brown, MD
role: STUDY_DIRECTOR
References: