Immunization With NY-ESO-1 Protein Combined With CpG 7909 in Patients With Prostate Cancer

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00292045
• Collaborator: (none)
• Enrollment: 15
• Locations: 2
• Arm: 1
• Actual Duration (Months): 14.4
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.5

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: NY-ESO-1 protein/CpG 7909	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 27, 2004
• Actual Primary Completion Date: Jan 9, 2006
• Actual Study Completion Date: Jan 9, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NY-ESO-1 protein + CpG 7909 Patients received immunization with intradermal injections of the NY-ESO-1 protein combined with CpG 7909.	Biological: NY-ESO-1 protein/CpG 7909; 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).

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Treatment-emergent Adverse Events (TEAEs) [Up to 56 weeks]

   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

1. Number of Patients With Cellular Antibody Response to NY-ESO-1 [Up to 28 weeks]

   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.

2. Number of Patients With Humoral Antibody Response to NY-ESO-1 [Up to 28 weeks]

   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.

3. Number of Patients With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST) [Up to 32 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria

Patients were eligible for enrollment if they fulfilled the following criteria:

1. High-risk Stage D1 or metastatic prostate cancer (D2), confirmed by review of histology.

2. Fully recovered from surgery.

3. 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.

4. 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.

5. Expected survival of ≥ 3 months.

6. Karnofsky performance status of ≥ 70%.

7. 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.

1. Age ≥ 18 years.

2. Able to give valid written informed consent.

Exclusion Criteria

Patients were excluded from the study if they fulfilled any of the following criteria:

1. 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).

2. Other serious illnesses, e.g., active infections requiring antibiotics, bleeding disorders.

3. Concomitant systemic treatment with corticosteroids. Topical or inhalational steroids were permitted.

4. Metastatic disease to the central nervous system.

5. 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.

6. Lack of availability for immunological and clinical follow-up assessments.

7. Participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to first dosing.

8. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krankenhaus Nordwest	Frankfurt		Germany
2	Universitätsspital Zürich	Zurich		Switzerland

Sponsors and Collaborators

• Ludwig Institute for Cancer Research

Investigators

• Principal Investigator: Alexander Knuth, MD, Clinic of Oncology, University Hospital Zürich, Switzerland
• Principal Investigator: Elke Jäger, MD, PhD, II. Medizinische Klinik, Hämatologie/Onkologie, Krankenhaus Nordwest, Frankfurt

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00292045
• Other Study ID Numbers: LUD2003-024; 2004DR1380 (SwissMedic); KEK-StV-Nr. 01/04 (local EC)
• First Posted: Feb 15, 2006
• Last Update Posted: Jan 27, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: NY-ESO-1 protein, immunization, advanced prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	NY-ESO-1 Protein + CpG 7909
Arm/Group 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). Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression.
Period Title: Core Study (Through Week 13)
STARTED	15
COMPLETED	13
NOT COMPLETED	2
Period Title: Core Study (Through Week 13)
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	NY-ESO-1 Protein + CpG 7909
Arm/Group 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). Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression.
Overall Participants	15
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	15 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	15 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 20%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 80%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Switzerland	3 20%
Germany	12 80%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The population comprises all patients who received any dose of study treatment.

Arm/Group Title	NY-ESO-1 Protein + CpG 7909
Arm/Group 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). Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression.
Measure Participants	15
Any TEAE	15 100%
Maximum TEAE severity Grade 1	2 13.3%
Maximum TEAE severity Grade 2	10 66.7%
Maximum TEAE severity Grade 3	2 13.3%
Maximum TEAE severity Grade 4	1 6.7%
Serious TEAE	4 26.7%
TEAE leading to discontinuation	1 6.7%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population comprises all patients who received at least 4 vaccinations with study treatment.

Arm/Group Title	NY-ESO-1 Protein + CpG 7909
Arm/Group 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). Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression.
Measure Participants	13
CD4+ T cell response	9 60%
CD8+ T cell response	6 40%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population comprises all patients who received at least 4 vaccinations with study treatment.

Arm/Group Title	NY-ESO-1 Protein + CpG 7909
Arm/Group 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). Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression.
Measure Participants	13
Count of Participants [Participants]	13 86.7%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population comprises all patients who received at least 4 vaccinations with study treatment.

Arm/Group Title	NY-ESO-1 Protein + CpG 7909
Arm/Group 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). Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression.
Measure Participants	13
Stable disease	8 53.3%
Progressive disease	3 20%
No evidence of disease at baseline and on study	2 13.3%

Adverse Events

Time Frame	All adverse events (AEs), regardless of causality to study drug, were documented from the first dose of study treatment through the final follow-up visit, for an AE collection period of up to 56 weeks for each patient.
Adverse Event Reporting Description	AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 3.0), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, preferred terms were counted only once per patient at the maximum reported grade.
Arm/Group Title	NY-ESO-1 Protein + CpG 7909
Arm/Group 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). Patients who demonstrated stable disease, minor response, partial response, or complete response at Week 13 may have continued to receive vaccinations until disease progression.
All Cause Mortality
	NY-ESO-1 Protein + CpG 7909
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	NY-ESO-1 Protein + CpG 7909
	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)
General disorders
Oedema peripheral	1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/15 (6.7%)
Nervous system disorders
Paraplegia	1/15 (6.7%)
Renal and urinary disorders
Urinary tract obstruction	1/15 (6.7%)
Renal failure	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/15 (6.7%)
Vascular disorders
Hypotension	1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	NY-ESO-1 Protein + CpG 7909
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Cardiac disorders
Bradycardia	1/15 (6.7%)
Tachycardia	1/15 (6.7%)
Eye disorders
Accommodation disorder	1/15 (6.7%)
Eye irritation	1/15 (6.7%)
Gastrointestinal disorders
Nausea	3/15 (20%)
Diarrhoea	1/15 (6.7%)
Flatulence	1/15 (6.7%)
General disorders
Injection site erythema	13/15 (86.7%)
Pyrexia	12/15 (80%)
Influenza like illness	4/15 (26.7%)
Chills	3/15 (20%)
Injection site pain	2/15 (13.3%)
Injection site vesicles	2/15 (13.3%)
Oedema peripheral	1/15 (6.7%)
Asthenia	1/15 (6.7%)
Feeling cold	1/15 (6.7%)
Injection site necrosis	1/15 (6.7%)
Non-cardiac chest pain	1/15 (6.7%)
Infections and infestations
Urinary tract infection	3/15 (20%)
Tooth infection	1/15 (6.7%)
Investigations
Weight decreased	2/15 (13.3%)
Aspartate aminotransferase increased	1/15 (6.7%)
Blood bilirubin increased	1/15 (6.7%)
C-reactive protein increased	1/15 (6.7%)
Karnofsky scale worsened	1/15 (6.7%)
Weight increased	1/15 (6.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/15 (20%)
Bone pain	2/15 (13.3%)
Myalgia	2/15 (13.3%)
Back pain	1/15 (6.7%)
Flank pain	1/15 (6.7%)
Musculoskeletal pain	1/15 (6.7%)
Osteoarthritis	1/15 (6.7%)
Pain in extremity	1/15 (6.7%)
Pain in jaw	1/15 (6.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma	1/15 (6.7%)
Nervous system disorders
Headache	4/15 (26.7%)
Sciatica	1/15 (6.7%)
Syncope	1/15 (6.7%)
Psychiatric disorders
Sleep disorder	1/15 (6.7%)
Renal and urinary disorders
Dysuria	2/15 (13.3%)
Nocturia	2/15 (13.3%)
Pollakiuria	2/15 (13.3%)
Bladder pain	1/15 (6.7%)
Haematuria	1/15 (6.7%)
Urinary retention	1/15 (6.7%)
Reproductive system and breast disorders
Pelvic pain	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/15 (13.3%)
Cough	1/15 (6.7%)
Oropharyngeal pain	1/15 (6.7%)
Sneezing	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Night sweats	2/15 (13.3%)
Rash	1/15 (6.7%)
Skin maceration	1/15 (6.7%)
Vascular disorders
Hypotension	2/15 (13.3%)
Deep vein thrombosis	1/15 (6.7%)
Hot flush	1/15 (6.7%)
Hypertension	1/15 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.