Back to resultsImmunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
NY-ESO-1 protein/CpG 7909
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring NY-ESO-1 protein, immunization, advanced prostate cancer
Eligibility Criteria
Inclusion Criteria Patients were eligible for enrollment if they fulfilled the following criteria: High-risk Stage D1 or metastatic prostate cancer (D2), confirmed by review of histology. Fully recovered from surgery. Showed stable or progressive disease as assessed by X-ray, ultrasound, and/or computed tomography (CT) scans under hormonal and/or chemotherapeutic treatment, which had been administered for ≥ 3 months. Any pretreatment with chemo- or radiotherapy must have been discontinued for ≥ 4 weeks prior to the first dose of study agent. Hormone therapy was allowed before and throughout the study. Expected survival of ≥ 3 months. Karnofsky performance status of ≥ 70%. Within the last 2 weeks prior to study day 1, vital laboratory parameters should have been within the normal range, except for the following laboratory parameters, which should have been within the ranges specified: Leukocytes > 3,000/µl. Lymphocytes > 700/µl. Platelets > 100,000/µl. Serum creatinine < 2.5 mg/dL. Alanine aminotransferase, aspartate aminotransferase, and total bilirubin < 2.5 x upper limit of normal. Age ≥ 18 years. Able to give valid written informed consent. Exclusion Criteria Patients were excluded from the study if they fulfilled any of the following criteria: Clinically significant heart disease (i.e., New York Heart Association Class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias). Other serious illnesses, e.g., active infections requiring antibiotics, bleeding disorders. Concomitant systemic treatment with corticosteroids. Topical or inhalational steroids were permitted. Metastatic disease to the central nervous system. Mental impairment, in the opinion of the Investigator, that may have compromised the ability to give informed consent and comply with the requirements of the study. Lack of availability for immunological and clinical follow-up assessments. Participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to first dosing. Being a recipient of an organ or bone marrow allograft. Having an autoimmune disease other than vitiligo, such as, but not limited to, inflammatory bowel disease or multiple sclerosis.
Sites / Locations
- Krankenhaus Nordwest
- Universitätsspital Zürich
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NY-ESO-1 protein + CpG 7909
Arm Description
Patients received immunization with intradermal injections of the NY-ESO-1 protein combined with CpG 7909.
Outcomes
Primary Outcome Measures
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the first dose of study treatment through the final follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Secondary Outcome Measures
Number of Patients With Cellular Antibody Response to NY-ESO-1
Assays to assess cluster of differentiation (CD)4+ and CD8+ antigen-specific responses were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 4, 10, 16, 22, and 28) by enzyme-linked immune absorbent spot (ELISPOT) assay. A positive response was considered if the number of spots in the peptide-exposed well was 2-fold or more higher than the number of spots in the unstimulated well, and if there was a minimum of 10 (after subtraction of background spots) peptide-specific spots/25.000 T cells or less if T-cell clones were used.
Number of Patients With Humoral Antibody Response to NY-ESO-1
Assays to assess NY-ESO-1 specific antibodies were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 4, 7, 10, 13, 16, 19, 22, 25, and 28). Sera were assessed over a range of dilutions from 1:100 to 1:400,000. Vaccine-induced antibodies were mapped with a panel of overlapping 20 mer peptides (25 μg/mL) spanning the whole protein sequence by enzyme-linked immunosorbent assay (ELISA). Immunoglobulin (Ig) subclasses G1 and G3 were determined by Western blot analysis using secondary antibody mouse anti-human IgG1/IgG3 at a dilution of 1:1000.
Number of Patients With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
Appropriate imaging scans were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 13 and 28). Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16). Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria.
Full Information
NCT ID
NCT00292045
First Posted
February 13, 2006
Last Updated
October 2, 2023
Sponsor
Ludwig Institute for Cancer Research
1. Study Identification
Unique Protocol Identification Number
NCT00292045
Brief Title
Immunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With Prostate Cancer
Official Title
Phase 1 Study of Immunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With High-risk Stage D1 or Advanced Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
October 27, 2004 (Actual)
Primary Completion Date
January 9, 2006 (Actual)
Study Completion Date
January 9, 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This was a Phase 1, open-label, fixed-dose study of immunization with the NY-ESO-1 protein combined with CpG 7909 as an adjuvant in patients with histopathologically confirmed, high-risk Stage D1 or advanced prostate cancer. The primary study objective was to assess the safety of NY-ESO-1 protein/CpG 7909 immunization, and the secondary objective was to evaluate the immunity induced by immunization.
Detailed Description
Eligible patients received vaccinations consisting of the NY-ESO-1 protein (100 µg) combined with CpG 7909 (2.5 mg) administered intradermally every 3 weeks for 4 doses. Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression. In patients with mixed response, single progressive lesions may have been resected and vaccination may have been continued.
Safety was monitored continuously. Blood samples were obtained for clinical hematology, biochemistry and immune response assessments, including antinuclear antibody (ANA) and anti-dsDNA, NY-ESO-1 and/or LAGE-1 specific antibodies, and NY-ESO-1 specific cluster of differentiation (CD)4+ and CD8+ T cells.
A tumor sample, resected prior to immunization, was tested to determine NY-ESO-1 and/or LAGE-1 expression. Delayed-type hypersensitivity (DTH) testing was performed at baseline and on study.
Disease status was assessed at baseline and on study in patients with measurable disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
NY-ESO-1 protein, immunization, advanced prostate cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NY-ESO-1 protein + CpG 7909
Arm Type
Experimental
Arm Description
Patients received immunization with intradermal injections of the NY-ESO-1 protein combined with CpG 7909.
Intervention Type
Biological
Intervention Name(s)
NY-ESO-1 protein/CpG 7909
Intervention Description
Patients received vaccinations consisting of the NY-ESO-1 protein (100 µg) combined with CpG 7909 (2.5 mg) as an adjuvant administered intradermally every 3 weeks for 4 doses (i.e., 12-week cycle).
Primary Outcome Measure Information:
Title
Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Description
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), and Grade 5 (fatal). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, performance status evaluations, and any other medically indicated assessments, including patient interviews, from the first dose of study treatment through the final follow-up visit. AEs were considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment.
Time Frame
Up to 56 weeks
Secondary Outcome Measure Information:
Title
Number of Patients With Cellular Antibody Response to NY-ESO-1
Description
Assays to assess cluster of differentiation (CD)4+ and CD8+ antigen-specific responses were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 4, 10, 16, 22, and 28) by enzyme-linked immune absorbent spot (ELISPOT) assay. A positive response was considered if the number of spots in the peptide-exposed well was 2-fold or more higher than the number of spots in the unstimulated well, and if there was a minimum of 10 (after subtraction of background spots) peptide-specific spots/25.000 T cells or less if T-cell clones were used.
Time Frame
Up to 28 weeks
Title
Number of Patients With Humoral Antibody Response to NY-ESO-1
Description
Assays to assess NY-ESO-1 specific antibodies were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 4, 7, 10, 13, 16, 19, 22, 25, and 28). Sera were assessed over a range of dilutions from 1:100 to 1:400,000. Vaccine-induced antibodies were mapped with a panel of overlapping 20 mer peptides (25 μg/mL) spanning the whole protein sequence by enzyme-linked immunosorbent assay (ELISA). Immunoglobulin (Ig) subclasses G1 and G3 were determined by Western blot analysis using secondary antibody mouse anti-human IgG1/IgG3 at a dilution of 1:1000.
Time Frame
Up to 28 weeks
Title
Number of Patients With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
Description
Appropriate imaging scans were performed at baseline (within 14 days prior to the first vaccination) and during the vaccination period (Weeks 13 and 28). Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16). Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria.
Time Frame
Up to 32 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patients were eligible for enrollment if they fulfilled the following criteria:
High-risk Stage D1 or metastatic prostate cancer (D2), confirmed by review of histology.
Fully recovered from surgery.
Showed stable or progressive disease as assessed by X-ray, ultrasound, and/or computed tomography (CT) scans under hormonal and/or chemotherapeutic treatment, which had been administered for ≥ 3 months.
Any pretreatment with chemo- or radiotherapy must have been discontinued for ≥ 4 weeks prior to the first dose of study agent. Hormone therapy was allowed before and throughout the study.
Expected survival of ≥ 3 months.
Karnofsky performance status of ≥ 70%.
Within the last 2 weeks prior to study day 1, vital laboratory parameters should have been within the normal range, except for the following laboratory parameters, which should have been within the ranges specified:
Leukocytes > 3,000/µl.
Lymphocytes > 700/µl.
Platelets > 100,000/µl.
Serum creatinine < 2.5 mg/dL.
Alanine aminotransferase, aspartate aminotransferase, and total bilirubin < 2.5 x upper limit of normal.
Age ≥ 18 years.
Able to give valid written informed consent.
Exclusion Criteria
Patients were excluded from the study if they fulfilled any of the following criteria:
Clinically significant heart disease (i.e., New York Heart Association Class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
Other serious illnesses, e.g., active infections requiring antibiotics, bleeding disorders.
Concomitant systemic treatment with corticosteroids. Topical or inhalational steroids were permitted.
Metastatic disease to the central nervous system.
Mental impairment, in the opinion of the Investigator, that may have compromised the ability to give informed consent and comply with the requirements of the study.
Lack of availability for immunological and clinical follow-up assessments.
Participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.
Being a recipient of an organ or bone marrow allograft. Having an autoimmune disease other than vitiligo, such as, but not limited to, inflammatory bowel disease or multiple sclerosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexander Knuth, MD
Organizational Affiliation
Clinic of Oncology, University Hospital Zürich, Switzerland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elke Jäger, MD, PhD
Organizational Affiliation
II. Medizinische Klinik, Hämatologie/Onkologie, Krankenhaus Nordwest, Frankfurt
Official's Role
Principal Investigator
Facility Information:
Facility Name
Krankenhaus Nordwest
City
Frankfurt
Country
Germany
Facility Name
Universitätsspital Zürich
City
Zurich
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
10655437
Citation
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
Results Reference
background
PubMed Identifier
21163871
Citation
Karbach J, Neumann A, Atmaca A, Wahle C, Brand K, von Boehmer L, Knuth A, Bender A, Ritter G, Old LJ, Jager E. Efficient in vivo priming by vaccination with recombinant NY-ESO-1 protein and CpG in antigen naive prostate cancer patients. Clin Cancer Res. 2011 Feb 15;17(4):861-70. doi: 10.1158/1078-0432.CCR-10-1811. Epub 2010 Dec 16.
Results Reference
result
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Immunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With Prostate Cancer
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