MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer
- Conditions
- Castrate Resistant Prostate Cancer (CRPC)
- Interventions
- Biological: BPX-101
- Registration Number
- NCT00868595
- Lead Sponsor
- Bellicum Pharmaceuticals
- Brief Summary
This is a Phase I, non-randomized, multiple-dose, 3+3 dose-escalation study of the safety, pharmacokinetics, biomarkers, preliminary efficacy and patient-reported outcomes of therapeutic vaccine, BPX-101 (formerly BP-GMAX-CD1), plus activating agent, AP1903, in patients with castrate resistant prostate cancer.
- Detailed Description
Patients will be screened within 6 weeks prior to Week 1. A total of 3 cohorts, consisting of 3 to 6 patients each, are planned to receive five to eight intradermal (ID) injections totaling 1 mL up to 1.6mL of BPX-101 at 3 doses levels for an initial 6 doses.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 18
- Males ≥ 18 years of age
- Histological diagnosis of adenocarcinoma of the prostate
- Documented evidence of distant metastasis of disease
- No more than 1 prior chemotherapeutic, biologic or combination treatment regimen (including vitamin D analogues) for CRPC. If previously treated, patients must be recovered from all toxicities prior to entry into the study.
- Patients must have current or historical evidence of disease progression concomitant with surgical (orchiectomy) or medical castration (LHRH analogue); anti-androgen withdrawal (4 weeks for flutamide and 6 weeks for nilutamide or bicalutamide) is necessary only for patients on antiandrogens and a duration of response to antiandrogens > 3months;
- Testosterone < 50 ng/dL achieved via medical or surgical castration. Patients receiving medical castration therapy must continue such therapy throughout the study.
- Adequate hematologic, renal and liver function:
- Negative serology tests for human immunodeficiency virus (HIV-1 and 2), human T-cell lymphotropic virus (HTLV-1), hepatitis B surface antigen (HBsAg) and hepatitis C (HCV)
- Karnofsky Performance Score (KPS) ≥ 70%
- Life expectancy > 6 months
- Written informed consent obtained prior to the initiation of study procedures
- The presence of brain metastases, pleural effusions or ascites
- Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or spinal cord compression
- A history of stage III or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the patient must be disease-free at the time of registration. Patients with a history of stage I or II other cancers must have been adequately treated and been disease-free for 3 years at the time of registration.
- More than 1 prior chemotherapy, biologic or combination treatment regimen (including vitamin D analogues) for CRPC
- Any treatment with radiopharmaceuticals, e.g. Strontium-89 and Samarium-153
- Ketoconazole or antiandrogens (flutamide, nilutamide, bicalutamide) within 2 weeks prior to registration. Patients who demonstrate an anti-androgen withdrawal response, defined as a > 25% drop in PSA within 4 weeks (flutamide) or 6 weeks (nilutamide, bicalutamide) of stopping a non-steroidal anti-androgen, are not eligible until the PSA rises above the nadir observed after anti-androgen withdrawal.
- Initiation of bisphosphonate therapy within 28 days prior to registration. Patients taking bisphosphonates should not have their dosing regimen altered unless medically warranted.
- A requirement for systemic steroid or other immunosuppressive therapy for any reason.
- Treatment with any of the following medications or interventions < 28 days prior to Screening
- Treatment with any investigational vaccine within 2 years prior to Screening, or treatment with any other investigational product within 28 days prior to Screening
- Any antibiotic therapy or infection within 1 week prior to Screening, including unexplained fever (temperature ≥ 100.5F or 38.1C)
- History of autoimmune disease
- Serious ongoing chronic or acute illness
- Any medical intervention or other condition which, in the opinion of the Principal Investigator and/or the Bellicum Medical Monitor, could compromise adherence with study requirements
Other Criteria Apply however are not listed
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose escalation BPX-101 Cohort 1: BPX-101, 4 x 10\*6 cells administered every other week for 6 cycles Cohort 2: BPX-101, 12.5 x 10\*6 cells administered every other week for 6 cycles Cohort 3: BPX-101, 25 x 10\*6 cells administered every other week for 6 cycles Cohort 4: BPX-101, 25 x 10\*6 cells administered every 4 weeks for 3 cycles At 24 hours after each vaccination, a single dose of the activating agent, AP1903 for Injection, will be administered at a fixed dose of 0.4 mg/kg via intravenous (IV) infusion over 2 hours. Dose escalation AP1903 Cohort 1: BPX-101, 4 x 10\*6 cells administered every other week for 6 cycles Cohort 2: BPX-101, 12.5 x 10\*6 cells administered every other week for 6 cycles Cohort 3: BPX-101, 25 x 10\*6 cells administered every other week for 6 cycles Cohort 4: BPX-101, 25 x 10\*6 cells administered every 4 weeks for 3 cycles At 24 hours after each vaccination, a single dose of the activating agent, AP1903 for Injection, will be administered at a fixed dose of 0.4 mg/kg via intravenous (IV) infusion over 2 hours.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of BPX-101 and AP1903 1 Year To determine the maximum tolerated dose (MTD) of BPX-101 and AP1903 when administered 24 hours apart
Safety and tolerability of BPX-101 and AP1903 1 Year To determine other measures of safety and tolerability of BPX-101 and AP1903 when administered 24 hours apart to patients with castrate resistant prostate cancer (CRPC).
- Secondary Outcome Measures
Name Time Method Number of circulating tumor cells (CTC) 1 Year To assess reduction in the number of circulating tumor cells (CTC)
Cancer-related pain 1 Year To assess cancer-related pain
Pain medication usage 1 Year To assess pain medication usage
Pharmacokinetics of AP1903 1 Year To determine the pharmacokinetics of AP1903 when administered 24 hours after BPX-101
Immune responses and their association with clinical outcome 2 Years To assess immune responses and their association with clinical outcome as measured by changes in levels of interferon gamma (IFN)-producing T cells, the cytotoxic T lymphocyte (CTL) response, cytokines (IFN, IL-4, IL-10), activation markers, and other markers
PSA response and PSA dynamics 1 Year To assess PSA response and PSA dynamics (change in velocity, doubling time)
Preliminary efficacy of BPX-101 at the maximum tolerated dose (MTD) 2 Years To determine preliminary efficacy of BPX-101 at the maximum tolerated dose (MTD), based on tumor assessments using computed tomography (CT) or magnetic resonance imaging (MRI) and radionuclide bone scans
Trial Locations
- Locations (1)
University of Texas Health Science Center Houston, CRU
🇺🇸Houston, Texas, United States