Safety Study of Adjuvant Vaccine to Treat Melanoma Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Ludwig Institute for Cancer Research
Oncovir, Inc.
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Dr. Nina Bhardwaj, Bhardwaj, Nina, M.D.
ClinicalTrials.gov Identifier:
NCT01079741
First received: March 2, 2010
Last updated: December 12, 2012
Last verified: December 2012
  Purpose

The incidence of melanoma is increasing with an estimated incidence of 59,940 cases and an annual death rate of 8110 in 2007. Although patients diagnosed with early stage disease have an excellent clinical outcome, patients diagnosed with advanced or recurrent disease, continue to have a high mortality rate, even with initial optimal surgical resection. Effective adjuvant strategies are needed to increase the time to progression and to decrease the recurrence rate. Immunotherapy has long been recognized as a potential therapy for melanoma; the goal of adjuvant vaccine therapy is to train the endogenous immune system to recognize and target minimal residual disease.


Condition Intervention Phase
Melanoma
Biological: NY-ESO-1 protein; Poly-ICLC; Montanide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/Phase II Open Label Study of the TLR3 Agonist Poly-ICLC as an Adjuvant for NY-ESO-1 Protein Vaccination With or Without Montanide ® ISA-51 VG in Patients With High Risk Melanoma in Complete Clinical Remission

Resource links provided by NLM:


Further study details as provided by Bhardwaj, Nina, M.D.:

Primary Outcome Measures:
  • Phase I, to define the safety of subcutaneous vaccination with NY-ESO-1 protein, Montanide and escalating doses of Poly-ICLC [ Time Frame: Disease status is assessed at baseline, wks 4 & 12 and after 4th vaccination (wks 14 & 22). At wk 52, disease status is assessed through patient follow-up with study physicians or through contact with the patient's regular treating physician. ] [ Designated as safety issue: Yes ]
    Up to 3 cohorts of 3 patients will be given a subcutaneous vaccination of 100µg NY-ESO-1 protein emulsified in 1.1mL Montanide® ISA-51VG (day 1) with escalating doses of Poly-ICLC. Dose-escalation will continue if no DLTs are observed in the 3 patients in a given cohort.


Secondary Outcome Measures:
  • To evaluate the induction of humoral and T cell (CD4+ and CD8+) immunity to subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given with or without Montanide. [ Time Frame: Disease status is assessed at baseline, wks 4 & 12 and after 4th vaccination (wks 14 & 22). At wk 52, disease status is assessed through patient follow-up with study physicians or through contact with the patient's regular treating physician. ] [ Designated as safety issue: No ]
    When Phase I is complete (no cohort 3 DLT observed) 24 new patients are randomized in Phase II to receive treatment under Arm A or Arm B. They receive s.c. vaccinations of 100μg NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A); or with 100μg NY-ESO-1 protein, Poly-ICLC dose TBD and 1.1mL Montanide (Arm B). Administrations occur every 3 wks on study wks 1,4,7,&10. Injections may occur w/in +/-3 days of planned date. Blood samples are obtained at baseline, 1 wk after vaccinations, and 1&3 months after last vaccination for assessment of NY-ESO-1 specific antibodies and CD4+ & CD8+ T cells.


Estimated Enrollment: 33
Study Start Date: September 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-escalation component
Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen and Montanide will be held constant.
Biological: NY-ESO-1 protein; Poly-ICLC; Montanide

Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen (100µg) and Montanide (1.1mL) will be held constant.

Phase II: The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B).

Other Names:
  • Cancer-Testis (CT) antigen expression: NY-ESO-1
  • Poly ICLC: carboxymethlycellulose, polyinosinic-polycytidylic acid & poly-L-lysine double-stranded RNA
  • Montanide® ISA-51 VG: mineral oil-based adjuvant; also called (IFA)incomplete Freund's adjuvant.
Active Comparator: Phase II is the randomized component.
The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B).
Biological: NY-ESO-1 protein; Poly-ICLC; Montanide

Phase I represents the dose-escalation component with Poly-ICLC given in combination with NY-ESO-1 and Montanide in an open-label fashion. The dose of Poly-ICLC will be increased stepwise from 0.35mg to 1.4mg while the dose of NY-ESO-1 antigen (100µg) and Montanide (1.1mL) will be held constant.

Phase II: The doses of NY-ESO-1 and Montanide will remain the same as in Phase I; the highest tolerated Phase I dose of Poly-ICLC will become the Phase II Poly-ICLC dose. In Phase II, patients will be randomized to a subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide (Arm B).

Other Names:
  • Cancer-Testis (CT) antigen expression: NY-ESO-1
  • Poly ICLC: carboxymethlycellulose, polyinosinic-polycytidylic acid & poly-L-lysine double-stranded RNA
  • Montanide® ISA-51 VG: mineral oil-based adjuvant; also called (IFA)incomplete Freund's adjuvant.

Detailed Description:

This is a Phase I open label dose escalation study of the TLR3 agonist Poly-ICLC as an adjuvant for NY-ESO-1 protein vaccination in patients with high risk melanoma in clinical complete remission (cCr), followed by a randomized Phase II component in which patients will be randomized to subcutaneous vaccination of NY-ESO-1 protein with Poly-ICLC alone dose TBD (Arm A) or with NY-ESO-1 protein, Poly-ICLC dose TBD and Montanide® ISA-51 VG (Montanide) (Arm B).

Patients with histological confirmed malignant melanoma, AJCC Stages: IIB, IIC, III or IV, who are in complete clinical remission (cCr) but at high risk of disease recurrence, will be eligible for enrollment, regardless of whether antigen expression in the autologous tumor can be demonstrated by either PCR or immunohistochemistry.

Primary Objectives:

  • Phase I: To define the safety of subcutaneous vaccination with NY-ESO-1 protein, Montanide and escalating doses of Poly-ICLC.
  • Phase II: To evaluate the induction of humoral and T cell (CD4+ and CD8+) immunity to subcutaneous vaccination with NY-ESO-1 protein in combination with Poly-ICLC when given with or without Montanide.

Exploratory analyses:

  • Evaluation of primary tumor expression of NY-ESO-1 by IHC or RT-PCR.
  • Histologic quantitation of original tumor TILs (tumor infiltrating lymphocytes), CD3+ cells, evaluation of mitotic index and correlation of this data with immunologic response.
  • Correlation of NY-ESO-1 specific T cell responses with HLA type
  • Investigation of polymorphisms for TLR3 through germline SNP analysis.
  • Clinical Outcome (Time to Progression) reported descriptively.
  • Skin section analysis of protein/adjuvant treated sites for immune cell infiltration and gene expression analysis
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Histological diagnosis of malignant melanoma, stages IIB-IV in radiologically confirmed cCr without clinical evidence of disease.
  2. At least 4 weeks since surgery prior to first dosing of study agent.
  3. Laboratory values within the following limits:

    1. Hemoglobin > 10.0 g/dL
    2. Neutrophil count > 1.5 x l09/L
    3. Lymphocyte count > Lower limit of institutional normal
    4. Platelet count > 80 x l09/L
    5. Serum creatinine < 2.0 mg/dL
    6. Serum bilirubin < 2 x upper limit of institutional normal
    7. AST/ALT < 2 x upper limit of institutional normal
  4. Patients must have an ECOG performance status of <2 (ECOG criteria published in [67].
  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).

Exclusion 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 within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.
  6. Prior chemotherapy or vaccine therapy.
  7. Radiation therapy, biological therapy or surgery within 4 weeks prior to first dose of study agent.
  8. Concomitant treatment with systemic corticosteroids greater than physiologic doses. Topical (but not at the proposed vaccination sites) or inhalational steroids are permitted.
  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. Psychiatric or addictive disorders that may compromise the ability to give informed consent.
  13. Lack of availability of the patient for immunological and clinical follow-up assessment.
  14. Children <18 years of age who cannot undergo the leukapheresis procedure, do not meet the disease staging and/or the size criteria for frequent blood donations
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01079741

Locations
United States, New York
New York University Langone Medical Center
New York, New York, United States, 10016
Sponsors and Collaborators
Dr. Nina Bhardwaj
Ludwig Institute for Cancer Research
Oncovir, Inc.
Cancer Research Institute, New York City
Investigators
Principal Investigator: Nina Bhardwaj, MD, PhD New York University Langone Medical Center
Principal Investigator: Anna Pavlick, D.O. New York University Langone Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Nina Bhardwaj, Director, Tumor Vaccine Program, Bhardwaj, Nina, M.D.
ClinicalTrials.gov Identifier: NCT01079741     History of Changes
Other Study ID Numbers: 09-0007
Study First Received: March 2, 2010
Last Updated: December 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Bhardwaj, Nina, M.D.:
Melanoma
Skin Cancer
Adjuvant Therapy
Oncogenesis
LAGE
Cancer Immunity
Neoplasms
Immunogenicity
Vaccine
Immunotherapy

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Poly I-C
Poly ICLC
Anti-Infective Agents
Antiviral Agents
Immunologic Factors
Interferon Inducers
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014