search
Back to results

Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

Primary Purpose

Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Extraocular Extension Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
gp100 antigen
tyrosinase peptide
recombinant MAGE-3.1 antigen
multi-epitope melanoma peptide vaccine
incomplete Freund's adjuvant
Montanide ISA 51 VG
agatolimod sodium
laboratory biomarker analysis
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ciliary Body and Choroid Melanoma, Medium/Large Size

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Stages IIC, III and IV cutaneous, or mucosal melanoma or stages III/IV ocular melanoma that have been completely resected; those rendered disease-free by radiation or systemic chemotherapy and/or immune therapy will also be eligible; patients must be entered within 12 months of disease-free status Patients must be positive for at least one of human leukocyte antigen (HLA) A1, A3/A11 typed by a standard deoxyribonucleic acid (DNA)-polymerase chain reaction (PCR) assay, and HLA-B44 status must be known; patients who are B44 positive but do not express A1, A3 or A11 are not eligible for this trial Tumor tissue must be available for analysis of gp100 and tyrosinase expression by immunohistochemistry; positive staining for at least one antigen will be an eligibility criteria for this trial Serum creatinine of 2.0 mg/dl or less Total bilirubin of 2.0 mg/dl or less Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) of 2.5 X institutional norm or less Total white blood cell (WBC) of 3,000 or more At least 1500 granulocytes Hemoglobin of 9.0 gm/dl Platelet count of 100,000 per cu mm Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients will be eligible for this trial if they have failed alpha-interferon, if it is felt to be contraindicated due to a pre-existing medical or psychiatric condition or if they have refused treatment with it Ability to read, understand and willingness to sign an institutional review board (IRB)-approved informed consent Exclusion Criteria: Who are undergoing or have undergone in the past month any other therapy for their cancer, including radiation therapy and adjuvant therapy; six weeks must have elapsed for nitrosoureas Have major systemic infections like pneumonia or sepsis, coagulation or bleeding disorders, or other major medical illnesses of the gastrointestinal, cardiovascular or respiratory systems Who require steroid therapy or have been treated with steroids within 4 weeks of starting the trial Who are pregnant or lactating, since the risk of autoimmune reactivity to tyrosinase or gp100 is felt to present a risk to the fetus or a breast feeding infant Who are known to be positive for hepatitis B surface antigen (BsAg), Hepatitis C antibody or human immunodeficiency virus (HIV) antibody; since cells removed for ex vivo handling and tissue culture cannot be virus positive, and the effects of 7909 might be detrimental to HIV positive patients, patients positive for the above viruses will not be treated on this trial Who have had a known allergic reaction to Montanide ISA 51 or ISA 51 VG Who have a prior history of uveitis, autoimmune inflammatory eye disease or other autoimmune diseases other than vitiligo or controlled thyroiditis Who have had another malignancy within the last three years with the exception of squamous or basal carcinoma of the skin or carcinoma in situ of the cervix that have been treated with curative intent Who have previously received any of the peptides in the vaccine

Sites / Locations

  • University of Southern California

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort I (melanoma peptide vaccine, Montanide ISA-51)

Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)

Arm Description

Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.

Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Immunologic response defined as either an enzyme-linked immunosorbent spot (ELISPOT) response or a tetramer response for at least one peptide

Secondary Outcome Measures

Toxicities of the vaccine preparation graded using Common Toxicity Criteria (CTC)
Will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTC criteria and nadir or maximum values for the laboratory measures), time of onset (i.e. weeks from initial peptide vaccination), duration, and reversibility or outcome.
Time to relapse
Will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol - for each cohort separately. To evaluate the association between immune response and time to recurrence and overall survival, the landmark method (at 26 weeks, the time of the 2nd leukapheresis for immune assessment) will be used and Kaplan-Meier curves will be calculated and the logrank test statistic will be calculated to compare the outcome of patients with or without an immunologic response.
Overall survival
Will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol - for each cohort separately. To evaluate the association between immune response and time to recurrence and overall survival, the landmark method (at 26 weeks, the time of the 2nd leukapheresis for immune assessment) will be used and Kaplan-Meier curves will be calculated and the logrank test statistic will be calculated to compare the outcome of patients with or without an immunologic response.

Full Information

First Posted
June 10, 2004
Last Updated
May 20, 2014
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00085189
Brief Title
Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma
Official Title
A PHASE II TRIAL OF A VACCINE COMBINING MULTIPLE CLASS I PEPTIDES WITH MONTANIDE ISA 51 OR ISA 51 VG AND CpG ADJUVANT 7909 FOR PATIENTS WITH RESECTED STAGES IIC/III AND IV MELANOMA
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
September 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This pilot phase II trial studies how well giving vaccine therapy works in treating patients with stage IIC-IV melanoma. Vaccines made from melanoma peptides or antigens may help the body build an effective immune response to kill tumor cells
Detailed Description
PRIMARY OBJECTIVES I. To perform a two-cohort, two-stage phase II two cohort pilot trial of a multi-peptide melanoma vaccine (multi-epitope melanoma peptide vaccine) with Montanide ISA 51 (incomplete Freund's adjuvant) or ISA 51 VG (Montanide ISA 51 VG) with adjuvant 7909 (agatolimod sodium) to define the safety and tolerability of each of the regimens, and to evaluate immune reactivity to a tyrosinase/gp100/MAGE-3 class I peptide vaccine combined with Montanide ISA 51 or ISA 51 VG with CpG adjuvant 7909 in human leukocyte antigen (HLA) class I A1, A3 or A11 and B44 matched patients with surgically resected stages IIC, III and IV melanoma. OUTLINE: Patients are assigned to 1 of 2 treatment cohorts. COHORT I: Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium subcutaneously (SC) at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity. COHORT II: Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 3 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size, Extraocular Extension Melanoma, Iris Melanoma, Metastatic Intraocular Melanoma, Mucosal Melanoma, Recurrent Intraocular Melanoma, Recurrent Melanoma, Stage IIC Melanoma, Stage IIIA Intraocular Melanoma, Stage IIIA Melanoma, Stage IIIB Intraocular Melanoma, Stage IIIB Melanoma, Stage IIIC Intraocular Melanoma, Stage IIIC Melanoma, Stage IV Intraocular Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (melanoma peptide vaccine, Montanide ISA-51)
Arm Type
Experimental
Arm Description
Patients receive multi-epitope peptide melanoma peptide vaccine with incomplete Freund's adjuvant and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Arm Title
Cohort II (melanoma peptide vaccine, Montanide ISA 51 VG)
Arm Type
Experimental
Arm Description
Patients receive multi-epitope peptide melanoma peptide vaccine with Montanide ISA 51 VG and agatolimod sodium SC at 0, 2, 4, 6, 8, 10, 14, 18, 22, 26, 38, and 50 weeks and then every six months for two years for up to 16 vaccinations in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
gp100 antigen
Other Intervention Name(s)
gp100
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
tyrosinase peptide
Other Intervention Name(s)
TYRP
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
recombinant MAGE-3.1 antigen
Other Intervention Name(s)
MAGE-3, MAGE-3.1, MAGEA3
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
multi-epitope melanoma peptide vaccine
Other Intervention Name(s)
MULTI-EP MP VAC
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
incomplete Freund's adjuvant
Other Intervention Name(s)
IFA, ISA-51, Montanide ISA 51
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Montanide ISA 51 VG
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
agatolimod sodium
Other Intervention Name(s)
CpG 7909, PF-3512676
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Immunologic response defined as either an enzyme-linked immunosorbent spot (ELISPOT) response or a tetramer response for at least one peptide
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Toxicities of the vaccine preparation graded using Common Toxicity Criteria (CTC)
Description
Will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTC criteria and nadir or maximum values for the laboratory measures), time of onset (i.e. weeks from initial peptide vaccination), duration, and reversibility or outcome.
Time Frame
Up to 3 years
Title
Time to relapse
Description
Will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol - for each cohort separately. To evaluate the association between immune response and time to recurrence and overall survival, the landmark method (at 26 weeks, the time of the 2nd leukapheresis for immune assessment) will be used and Kaplan-Meier curves will be calculated and the logrank test statistic will be calculated to compare the outcome of patients with or without an immunologic response.
Time Frame
Up to 3 years
Title
Overall survival
Description
Will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol - for each cohort separately. To evaluate the association between immune response and time to recurrence and overall survival, the landmark method (at 26 weeks, the time of the 2nd leukapheresis for immune assessment) will be used and Kaplan-Meier curves will be calculated and the logrank test statistic will be calculated to compare the outcome of patients with or without an immunologic response.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Stages IIC, III and IV cutaneous, or mucosal melanoma or stages III/IV ocular melanoma that have been completely resected; those rendered disease-free by radiation or systemic chemotherapy and/or immune therapy will also be eligible; patients must be entered within 12 months of disease-free status Patients must be positive for at least one of human leukocyte antigen (HLA) A1, A3/A11 typed by a standard deoxyribonucleic acid (DNA)-polymerase chain reaction (PCR) assay, and HLA-B44 status must be known; patients who are B44 positive but do not express A1, A3 or A11 are not eligible for this trial Tumor tissue must be available for analysis of gp100 and tyrosinase expression by immunohistochemistry; positive staining for at least one antigen will be an eligibility criteria for this trial Serum creatinine of 2.0 mg/dl or less Total bilirubin of 2.0 mg/dl or less Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) of 2.5 X institutional norm or less Total white blood cell (WBC) of 3,000 or more At least 1500 granulocytes Hemoglobin of 9.0 gm/dl Platelet count of 100,000 per cu mm Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Patients will be eligible for this trial if they have failed alpha-interferon, if it is felt to be contraindicated due to a pre-existing medical or psychiatric condition or if they have refused treatment with it Ability to read, understand and willingness to sign an institutional review board (IRB)-approved informed consent Exclusion Criteria: Who are undergoing or have undergone in the past month any other therapy for their cancer, including radiation therapy and adjuvant therapy; six weeks must have elapsed for nitrosoureas Have major systemic infections like pneumonia or sepsis, coagulation or bleeding disorders, or other major medical illnesses of the gastrointestinal, cardiovascular or respiratory systems Who require steroid therapy or have been treated with steroids within 4 weeks of starting the trial Who are pregnant or lactating, since the risk of autoimmune reactivity to tyrosinase or gp100 is felt to present a risk to the fetus or a breast feeding infant Who are known to be positive for hepatitis B surface antigen (BsAg), Hepatitis C antibody or human immunodeficiency virus (HIV) antibody; since cells removed for ex vivo handling and tissue culture cannot be virus positive, and the effects of 7909 might be detrimental to HIV positive patients, patients positive for the above viruses will not be treated on this trial Who have had a known allergic reaction to Montanide ISA 51 or ISA 51 VG Who have a prior history of uveitis, autoimmune inflammatory eye disease or other autoimmune diseases other than vitiligo or controlled thyroiditis Who have had another malignancy within the last three years with the exception of squamous or basal carcinoma of the skin or carcinoma in situ of the cervix that have been treated with curative intent Who have previously received any of the peptides in the vaccine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Weber
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033-0804
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

We'll reach out to this number within 24 hrs