NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine

Study Overview
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Brief Summary
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To evaluate the safety of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine given by particle-mediated epidermal delivery (PMED) in patients with tumor types known to express NY-ESO-1 or LAGE-1.

Detailed Description
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NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 4 microgram dosage of NY-ESO-1 was administered as 4 X 1 microgram PMEDs in close proximity. Similarly, the 8 microgram dosage was administered as 8 X 1 microgram PMEDs. The third cohort of patients received the 8 microgram dosage as a cluster dosage of 4 doses (day 1, 3, 5, 8) as 2 X 1 microgram PMEDs per day. Blood samples were to be obtained at baseline, 2 weeks after each vaccination, prior to the second and third vaccination, and 4 weeks after the third vaccination for the assessment of clinical hematology, biochemistry measurements and immunology responses. Patients were to be evaluated for toxicity throughout the study. Delayed-type hypersensitivity (DTH) testing was to be performed at baseline and at the 2-week visit following the first and third vaccinations. NY-ESO-1 and/or LAGE-1 specific antibodies were to be assessed in all patients by an enzyme-linked immunosorbent assay (ELISA). NY-ESO-1 specific CD4+ and CD8+ T-cells were to be assessed in all patients by tetramer and/or ELISPOT assays. Disease status was to be assessed at baseline and 4 weeks after the third vaccination in patients with measurable disease.

Official Title
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Safety and Immunological Evaluation of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine Given by Particle-mediated Epidermal Delivery (PMED) in Patients With Tumor Type Known to Express NY-ESO-1 or LAGE-1 Antigen.

Conditions
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Prostate Cancer, Bladder Cancer, Non-small Cell Lung Cancer, Esophageal Cancer, Sarcoma

Intervention / Treatment
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* Biological: NY-ESO-1 Plasmid DNA Cancer Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were eligible for enrollment if they fulfilled all of the following criteria: Histologically proven tumor type known to express NY-ESO-1 or LAGE-1 (prostate cancer, breast cancer, bladder cancer, hepatocellular cancer, synovial sarcoma, leiomyosarcoma, head and neck, lung cancer, esophageal, ovarian, neuroblastoma); or NY-ESO-1 or LAGE-1 positive tumors determined by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry or expression of LAGE-1 by RT-PCR. Advanced disease and have declined, delayed, failed or completed standard therapy. Full recovery from surgery. Expected survival of at least 6 months. Karnofsky performance scale ≥ 60. Adequate bone marrow, kidney, liver and immune functions. Able and willing to give valid written informed consent. Exclusion Criteria: Clinically significant heart disease (NYHA Class III or IV). Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders, clinically significant liver or renal insufficiency requiring treatment. Patients with serious intercurrent illness, requiring hospitalization. Known HIV, Hepatitis B or Hepatitis C positivity. History of autoimmune diseases (e.g. SLE, scleroderma). Vitiligo is not an exclusion criterion. Concomitant systemic treatment with corticosteroids, anti-histaminic drugs or non-steroidal anti-inflammatory drugs. Specific COX-2 inhibitors are permitted. Low dose aspirin is permitted. Topical or inhalational steroids are permitted. Evidence of skin disease (e.g. psoriasis, eczema or keloid formation) at the proposed administration site. Allergy to gold (including gold jewelry). History or evidence of chrysotherapy (gold salts). Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing (6 weeks for nitrosoureas). Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer, cervical carcinoma in situ. Mental impairment, in the opinion of the investigator, that may compromise 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 any other clinical trial involving another investigational agent within 4 weeks prior to first dosing. Pregnancy or breastfeeding. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>4 µg NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 4 µg dosage of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered as 4 X 1 µg PMEDs in close proximity. The vaccine was administered in weeks 1, 5, and 9 of Cycle 1. In the absence of > Grade 3 toxicity and in the absence of progressive disease requiring other treatment or the presence of NY-ESO-1 immunity, patients could receive an additional cycle of vaccinations of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine. | Biological: NY-ESO-1 Plasmid DNA Cancer Vaccine<br>* NY-ESO-1 Plasmid DNA Cancer Vaccine administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device.<br>|
| Experimental: Cohort 2<br>8 µg NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 8 µg dosage of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered as 8 X 1 µg PMEDs. The vaccine was administered in weeks 1, 5, and 9 of Cycle 1. In the absence of > Grade 3 toxicity and in the absence of progressive disease requiring other treatment or the presence of NY-ESO-1 immunity, patients could receive an additional cycle of vaccinations of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine. | Biological: NY-ESO-1 Plasmid DNA Cancer Vaccine<br>* NY-ESO-1 Plasmid DNA Cancer Vaccine administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device.<br>|
| Experimental: Cohort 3<br>8 µg NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device. The 8 µg dosage of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine was administered as a cluster dosage of 4 doses (day 1, 3, 5, 8) as 2 X 1 µg PMEDs per day. The vaccine was administered in weeks 1, 5, and 9 of Cycle 1. In the absence of > grade 3 toxicity and in the absence of progressive disease requiring other treatment or the presence of NY-ESO-1 immunity, patients could receive an additional cycle of vaccinations of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine. | Biological: NY-ESO-1 Plasmid DNA Cancer Vaccine<br>* NY-ESO-1 Plasmid DNA Cancer Vaccine administered by particle-mediated epidermal delivery (PMED) at a pressure of 500 psi using the XR-1 Powderject® delivery device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Dose Limiting Toxicities (DLTs) and Number of Patients With Adverse Events | All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 3.0, published June 10, 2003). DLT was defined as ≥ Grade 2 autoimmune phenomena Asymptomatic bronchospasm or generalized urticaria Grade ≥ non hematological toxicities (including injection site reactions) Grade ≥ 3 hematological toxicities A dose-limiting adverse event must be definitely, probably, or possibly related to the administration of the investigational agent and must occur between first dose and 4 weeks after the last dose. | up to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Tumor Response According to the Response Evaluation Criteria in Solid Tumors (RECIST). | Tumor response was assessed in patients with measurable tumors according to the Response Evaluation Criteria in Solid Tumors (RECIST). Computed tomography (CT) scans were performed at screening and at week 13. 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; no evidence of disease (NED): no new lesions in patients who did not have target lesions at baseline. | 13 weeks | 
| Number of Patients With NY-ESO-1-Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline. | Blood samples were obtained at baseline (prior to the first dose), and in weeks 3, 5, 7, 9, 11 and 13 for the assessment of NY-ESO-1-specific antibodies by an enzyme-linked immunosorbent assay (ELISA). A positive response was a readable optical density at 280 nm. | up to 13 weeks | 
| Number of Patients With NY-ESO-1-Specific Cellular Immunity as Measured by an Increase in NY-ESO-1-Specific CD4+ and CD8+ T-Cells Following Treatment. | Blood samples were obtained at baseline (prior to the first dose), and in weeks 3, 5, 7, 9, 11 and 13 for the assessment of NY-ESO-1-specific CD4+ and CD8+ T-cell responses by ELISPOT. | up to 13 weeks | 
| Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1 Protein | Delayed-Type Hypersensitivity (DTH) testing was conducted at baseline and on days 15 and 72 of the study. A positive DTH reaction to NY-ESO-1 protein at baseline was absent in all patients. The presence of redness and induration was considered necessary for a positive DTH reaction. | Up to 11 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NY-ESO-1, DNA