MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose escalation 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. |
Biological: BPX-101
Vaccine
Other Names:
Drug: AP1903
Activating agent, infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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)
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males ≥ 18 years of age
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Histological diagnosis of adenocarcinoma of the prostate
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Documented evidence of distant metastasis of disease
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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.
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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;
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Testosterone < 50 ng/dL achieved via medical or surgical castration. Patients receiving medical castration therapy must continue such therapy throughout the study.
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Adequate hematologic, renal and liver function:
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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)
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Karnofsky Performance Score (KPS) ≥ 70%
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Life expectancy > 6 months
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Written informed consent obtained prior to the initiation of study procedures
Exclusion Criteria:
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The presence of brain metastases, pleural effusions or ascites
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Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or spinal cord compression
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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.
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More than 1 prior chemotherapy, biologic or combination treatment regimen (including vitamin D analogues) for CRPC
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Any treatment with radiopharmaceuticals, e.g. Strontium-89 and Samarium-153
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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.
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Initiation of bisphosphonate therapy within 28 days prior to registration. Patients taking bisphosphonates should not have their dosing regimen altered unless medically warranted.
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A requirement for systemic steroid or other immunosuppressive therapy for any reason.
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Treatment with any of the following medications or interventions < 28 days prior to Screening
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Treatment with any investigational vaccine within 2 years prior to Screening, or treatment with any other investigational product within 28 days prior to Screening
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Any antibiotic therapy or infection within 1 week prior to Screening, including unexplained fever (temperature ≥ 100.5F or 38.1C)
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History of autoimmune disease
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Serious ongoing chronic or acute illness
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas Health Science Center Houston, CRU | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Bellicum Pharmaceuticals
- M.D. Anderson Cancer Center
- The University of Texas Health Science Center, Houston
- Memorial Hermann Hospital
- Baylor College of Medicine
Investigators
- Principal Investigator: Guru Sonpavde, MD, University of Texas Health Science Center Houston - CCTS
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- BP-PC-001