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Randomized, Double Blind, Placebo-controlled Topical Resiquimod Adjuvant for NY-ESO-1 Protein Vaccination

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ClinicalTrials.gov Identifier: NCT00821652
Recruitment Status : Completed
First Posted : January 13, 2009
Last Update Posted : January 8, 2015
Sponsor:
Collaborator:
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Nina Bhardwaj, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE January 12, 2009
First Posted Date  ICMJE January 13, 2009
Last Update Posted Date January 8, 2015
Study Start Date  ICMJE February 2009
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2009)
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. ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 12, 2009)
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 last study visit. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2009)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2009)
Evaluate if patients develop a delayed type hypersensitivity reaction to NY-ESO-1 protein after vaccination via skin biopsies obtained from the DTH site. [ Time Frame: Skin biopsies will be obtained after the last vaccination cycle. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized, Double Blind, Placebo-controlled Topical Resiquimod Adjuvant for NY-ESO-1 Protein Vaccination
Official Title  ICMJE 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
Brief Summary The study is designed to see if a course of injections containing the NY-ESO-1 protein (a tumor antigen, marker expressed by tumors); in combination with an immune stimulant (adjuvant) Montanide, with or without resiquimod (another adjuvant) is well tolerated and safe in patients with surgically resected Stage IIB, IIC, Stage III or Stage IV (AJCC criteria) melanoma, a tumor that expresses NY-ESO-1. In addition, this study is designed to see if the patient's body's defense (immune) system can be boosted (strengthened) by this vaccine and if the addition of resiquimod to the vaccine makes this more likely.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Tumors
Intervention  ICMJE
  • Drug: NY-ESO-1 protein; Montanide ISA®-51 VG; Resiquimod
    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.
  • Drug: NY-ESO-1 protein; Montanide ISA®-51 VG; Resiquimod/placebo
    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.
Study Arms  ICMJE
  • Dose-esclation
    Part I represents a dose-escalation part with topical resiquimod in an open-label fashion.
    Intervention: Drug: NY-ESO-1 protein; Montanide ISA®-51 VG; Resiquimod
  • 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.
    Intervention: Drug: NY-ESO-1 protein; Montanide ISA®-51 VG; Resiquimod/placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 12, 2009)
26
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

Patients will be eligible for enrollment if they fulfill the following criteria:

  1. 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
  2. At least 4 weeks since surgery prior to first dosing of study agent.
  3. 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

  4. Patients must have an ECOG performance status of <2 (ECOG criteria published in [46])
  5. Life expectancy > 6 months.
  6. Age > 18 years.
  7. Able and willing to give written informed consent for participation in the trial (see Section 12.2)
  8. 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:

  1. Serious illnesses, e.g., serious infections requiring antibiotics.
  2. Previous bone marrow or stem cell transplant.
  3. History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo.
  4. Metastatic disease to the central nervous system.
  5. Other malignancy prior to entry into the study.
  6. No radiation therapy, prior biological therapy or surgery within 4 weeks prior to first dose of study agent.
  7. No prior chemotherapy or prior vaccine or immunotherapy.
  8. 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'.)
  9. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
  10. Pregnancy or lactation.
  11. Women of childbearing potential not using a medically acceptable means of contraception.
  12. Patients with known history of inflammatory skin disorders (e.g.,psoriasis, lupus) that may be exacerbated by Resiquimod.
  13. Psychiatric or addictive disorders that may compromise the ability to give informed consent.
  14. Lack of availability of the patient for immunological and clinical follow-up assessment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00821652
Other Study ID Numbers  ICMJE GCO 13-1390
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nina Bhardwaj, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Nina Bhardwaj
Collaborators  ICMJE Cancer Research Institute, New York City
Investigators  ICMJE
Principal Investigator: Nina Bhardwaj, MD, PhD Icahn School of Medicine at Mount Sinai
Study Director: Rachel Sabado, PhD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP