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
Brief SummaryThis is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide.
Detailed DescriptionThis 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.
PhasePhase 2 - takes the treatment one step further, assessing the activity of a particular therapy in a disease, often building upon leads from the Phase I trial. While patients are generally required to be previously untreated, participation in a Phase II trial doesn't usually preclude the patient from getting the standard treatment after they've received the investigational agent. At best they are allowed to get a new drug they wouldn't be able to get otherwise that may turn out to be better for their disease.
Inclusion and Exclusion 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.
- 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
- Urological Associates of Southern Arizona, P.C., Tucson, Arizona, 85741
- The Urology Center of Colorado, Denver, Colorado, 80211
- Northwest Medical Specialties, Rainier Physicians, Tacoma, Washington, 98405
- Virginia Mason Medical Center, Virginia Mason Hospital, Seattle, Washington, 98101
- GU Research Network, Omaha, Nebraska, 68130
- Uro Partners/ RMD Clinical Research, Melrose Park, Illinois, 60160
- Urology Associates, PC, Nashville, Tennessee, 37209