- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00821652
Randomized, Double Blind, Placebo-controlled Topical Resiquimod Adjuvant for NY-ESO-1 Protein Vaccination
Phase I Randomized, Double-blind, Placebo-controlled Study of Topical Resiquimod as an Adjuvant for NY-ESO1 Protein+Montanide Vaccination in Patients With Tumors That Often Express NY-ESO-1
Study Overview
Status
Conditions
Detailed Description
There is no published data on the application of topical resiquimod in combination with an antigen in Montanide, therefore, this study includes a 2-part design where Part I represents a dose-escalation part with topical resiquimod in an open-label fashion. Part II represents the randomized part.
In Part I, 2 cohorts are planned: If no dose-limiting toxicity (DLT) occurs by day 8 of the last vaccination cycle in the last patient enrolled the first cohort, 3 additional patients (cohort 2) will be enrolled. If no DLT occurs by day 8 of the last vaccination cycle in the last patient enrolled the second cohort in Part I, the trial will proceed to Part II where patients will be randomized.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
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New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
Patients will be eligible for enrollment if they fulfill the following criteria:
- Histological diagnosis of surgically resected Stage IIB, IIC, Stage III or Stage IV (AJCC criteria) melanoma independent of NY-ESO-1 expression in a tumor biopsy
- At least 4 weeks since surgery prior to first dosing of study agent.
Laboratory values within the following limits:
Hemoglobin > 10.0 g/dL Neutrophil count > 1.5 x l09/L Lymphocyte count > Lower limit of institutional normal Platelet count > 80 x l09/L Serum creatinine < 2.0 mg/dL Serum bilirubin < 2 x upper limit of institutional normal AST/ALT < 2 x upper limit of institutional normal
- Patients must have an ECOG performance status of <2 (ECOG criteria published in [46])
- Life expectancy > 6 months.
- Age > 18 years.
- Able and willing to give written informed consent for participation in the trial (see Section 12.2)
- Patients enrolled in the adjuvant setting must have received standard curative therapy, e.g., surgery, radiation. Alternatively, patients can enter after refusing standard curative therapy only if therapy was clearly discussed with the treating physician or if they have failed another biologic therapy due to toxicity.
Exclusion Criteria
Patients will be excluded from the study if they fulfill any of the following criteria:
- Serious illnesses, e.g., serious infections requiring antibiotics.
- Previous bone marrow or stem cell transplant.
- History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo.
- Metastatic disease to the central nervous system.
- Other malignancy prior to entry into the study.
- No radiation therapy, prior biological therapy or surgery within 4 weeks prior to first dose of study agent.
- No prior chemotherapy or prior vaccine or immunotherapy.
- Concomitant treatment with systemic corticosteroids greater than physiologic doses. Topical (but not at the proposed vaccination sites) or inhalational steroids are permitted. (See also Section 6.7 for restrictions/recommendations on 'Ancillary Therapy'.)
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
- Pregnancy or lactation.
- Women of childbearing potential not using a medically acceptable means of contraception.
- Patients with known history of inflammatory skin disorders (e.g.,psoriasis, lupus) that may be exacerbated by Resiquimod.
- Psychiatric or addictive disorders that may compromise the ability to give informed consent.
- Lack of availability of the patient for immunological and clinical follow-up assessment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Dose-esclation
Part I represents a dose-escalation part with topical resiquimod in an open-label fashion.
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Part I: a cohort of 3 patients to receive a subcutaneous vaccination of 100µg NY-ESO-1 protein emulsified in 1.25mL Montanide ISA®-51 VG (day 1) followed by topical resiquimod 1000 mg of the 0.2% gel on days 1, and 3.
If no DLT observed, we will proceed to cohort 2 with Resiquimod dosing on days 1,3 and 5.
If DLT is found in the second cohort, the trial will proceed to Part II; with the limited dosing for days 1 and 3 only, as used in the first cohort.
If no DLT is found in second cohort, the trial will proceed to Part II with Resiquimod dosing for days1, 3 and 5.
|
Experimental: 2
Part II: Eligible patients will be randomized to receive a subcutaneous vaccination of 100µg NY-ESO-1 protein emulsified in 1.25mL Montanide ISA®-51 VG (day 1) followed by topical placebo gel (Arm A) or topical resiquimod gel (Arm B) on days 1, 3 and 5; or resiquimod dosing regimen established in Part I.
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Part II: Eligible patients will be randomized to receive a subcutaneous vaccination of 100µg NY-ESO-1 protein emulsified in 1.25mL Montanide ISA®-51 VG (day 1) followed by topical placebo gel (Arm A) or topical resiquimod gel (Arm B) on days 1, 3 and 5; or resiquimod dosing regimen established in Part I.
The cycles will be repeated every 3 weeks for a total of 4 cycles (on Study week 1, 4, 7 and 10).
All procedures may occur within + 3 days of the planned date.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The primary objectives of the study are to define the safety and immunogenicity of vaccination with NY-ESO-1 protein emulsified in Montanide® ISA-51 VG when given with or without the topical TLR 7/8 agonist resiquimod.
Time Frame: Blood samples are obtained at baseline, 1 week after each vaccination, and at follow-up 1visit.
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Blood samples are obtained at baseline, 1 week after each vaccination, and at follow-up 1visit.
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To document tumor response by RECIST criteria if applicable. Skin section analysis of resiquimod/placebo treated site for immune cell infiltration and gene expression analysis. Investigation of polymorphisms for TLR7/8 through germline SNP analysis
Time Frame: Skin biopsies will be obtained after the last vaccination cycle. Clinical hematology and biochemistry measurements will be taken at baseline, one week after the second vaccination and two to four weeks after the fourth vaccination
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Skin biopsies will be obtained after the last vaccination cycle. Clinical hematology and biochemistry measurements will be taken at baseline, one week after the second vaccination and two to four weeks after the fourth vaccination
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Rachel Sabado, PhD, Icahn School of Medicine at Mount Sinai
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GCO 13-1390
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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