MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer

This study has been completed.
Sponsor:
Collaborators:
M.D. Anderson Cancer Center
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston
Memorial Hermann Hospital
Baylor College of Medicine
Information provided by (Responsible Party):
Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00868595
First received: March 24, 2009
Last updated: July 24, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Castrate Resistant Prostate Cancer (CRPC)
Biological: BPX-101
Drug: AP1903
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Non-randomized, Multiple Dose, Dose Escalation Study of the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Therapeutic Vaccine, BP-GMAX-CD1, Plus Activating Agent, AP1903, in Patients With Castrate Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Bellicum Pharmaceuticals:

Primary Outcome Measures:
  • To determine the maximum tolerated dose (MTD) of BPX-101 and AP1903 when administered 24 hours apart [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
  • 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). [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the pharmacokinetics of AP1903 when administered 24 hours after BPX-101 [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
  • To assess PSA response and PSA dynamics (change in velocity, doubling time) [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • To assess reduction in the number of circulating tumor cells (CTC) [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • To assess cancer-related pain [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • To assess pain medication usage [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: April 2009
Study Completion Date: March 2012
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Every Other Week Schedule

Every Other Week Schedule:

Cohort 1: BPX-101, 4 x 10*6 cells Cohort 2: BPX-101, 12.5 x 10*6 cells Cohort 3: BPX-101, 25 x 10*6 cells

In Cohort 1 and Cohort 2, 1 mL of BP-GMAX-CD1 will be administered at each treatment visit as 5 intradermal (ID) injections (200 µL each). In Cohort 3, 1.6 mL of BP-GMAX-CD1 will be administered at each treatment visit as 8 intradermal (ID) injections (200 µL each). Each subject will receive an initial 6 doses, followed by boosters every 8 weeks for patients who do not progress. 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 Name: N/Ap
Drug: AP1903
Activating agent, infusion
Other Name: N/Ap
Experimental: Cohort 4

Cohort 4: BP-GMAX-CD1, 25 x 106 cells in 1.6 mL (as established as MTD in Cohort 3).

In Cohort 4, 1.6 mL of BP-GMAX-CD1 will be administered at each treatment visit as 8 ID injections (200 µL each), once every 4 weeks for 3 cycles (Q4W x 3). For Cohort 4 only, at least 2 patients should be enrolled who had not received prior treatment with Taxotere, and at least 3 patients should be enrolled who had received prior treatment with Taxotere.

Biological: BPX-101
Vaccine
Other Name: N/Ap
Drug: AP1903
Activating agent, infusion
Other Name: N/Ap

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males ≥ 18 years of age
  2. Histological diagnosis of adenocarcinoma of the prostate
  3. Documented evidence of distant metastasis of disease
  4. 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.
  5. 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;
  6. Testosterone < 50 ng/dL achieved via medical or surgical castration. Patients receiving medical castration therapy must continue such therapy throughout the study.
  7. Adequate hematologic, renal and liver function:
  8. 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)
  9. Karnofsky Performance Score (KPS) ≥ 70%
  10. Life expectancy > 6 months
  11. Written informed consent obtained prior to the initiation of study procedures

Exclusion Criteria:

  1. The presence of brain metastases, pleural effusions or ascites
  2. Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or spinal cord compression
  3. 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.
  4. More than 1 prior chemotherapy, biologic or combination treatment regimen (including vitamin D analogues) for CRPC
  5. Any treatment with radiopharmaceuticals, e.g. Strontium-89 and Samarium-153
  6. 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.
  7. Initiation of bisphosphonate therapy within 28 days prior to registration. Patients taking bisphosphonates should not have their dosing regimen altered unless medically warranted.
  8. A requirement for systemic steroid or other immunosuppressive therapy for any reason.
  9. Treatment with any of the following medications or interventions < 28 days prior to Screening
  10. Treatment with any investigational vaccine within 2 years prior to Screening, or treatment with any other investigational product within 28 days prior to Screening
  11. Any antibiotic therapy or infection within 1 week prior to Screening, including unexplained fever (temperature ≥ 100.5F or 38.1C)
  12. History of autoimmune disease
  13. Serious ongoing chronic or acute illness
  14. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868595

Locations
United States, Texas
University of Texas Health Science Center Houston, CRU
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bellicum Pharmaceuticals
M.D. Anderson Cancer Center
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston
Memorial Hermann Hospital
Baylor College of Medicine
Investigators
Principal Investigator: Guru Sonpavde, MD University of Texas Health Science Center Houston - CCTS
  More Information

Additional Information:
No publications provided

Responsible Party: Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00868595     History of Changes
Other Study ID Numbers: BP-PC-001
Study First Received: March 24, 2009
Last Updated: July 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 29, 2014