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Vaccine Therapy With or Without Sargramostim in Treating Patients Who Have Undergone Surgery for Melanoma

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
tyrosinase peptide
gp100 antigen
MART-1 antigen
incomplete Freund's adjuvant
Montanide ISA 51 VG
sargramostim
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
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

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

Inclusion Criteria: Patients who have completed protocol 10M-01-1 or 10M-00-4 are eligible for this study provided that They have received all injections with evidence of an immune response They have not experienced recurrence of the melanoma Not more than twelve months have elapsed since the final injection on either protocol They experienced no grade 3 or 4 toxicity attributed to the prior vaccine regimen Serum creatinine of 2.0 mg/dl or less Total bilirubin of 2.0 mg/dl or less SGOT/SGPT of 2.5 X institutional norm or less Total WBC of 3,000 or more At least 1500 granulocytes Hemoglobin of 9.0 gm/dl or more Platelet count of 100,000 per cu mm. or more 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 IRB-approved informed consent Patients who have had another malignancy but with no evidence of disease for greater than 5 years from accrual to the current trial will be eligible if it is felt they are likely to be cured; patients with squamous or basal carcinoma of the skin or carcinoma in situ of the cervix that have been treated with curative intent can be accrued to this trial 30 days after treatment Exclusion Criteria: Who have undergone any other systemic therapy for their melanoma, including radiation therapy since completion of 10M-01-1 or 10M-00-4 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 systemic, ocular or inhaled corticosteroids Who are pregnant or lactating, since the risk of autoimmune reactivity to tyrosinase, MART-1 or gp100 is felt to present a risk to the fetus or a breast feeding infant; effective birth control for men and women is required during and for four months after the study is finished Who are known to be positive for hepatitis BsAg, hepatitis C antibody or HIV antibody; since cells removed for ex vivo handling and tissue culture cannot be virus positive, and the effects of melanoma peptides 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 GM-CSF, Montanide ISA 51 (IFA) or any of the peptides included in this protocol Who have a prior history of uveitis or autoimmune inflammatory eye disease, immune hemolytic anemia or other active autoimmune disease

Sites / Locations

  • University of Southern California

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (vaccine therapy)

Arm II (vaccine therapy, sargramostim)

Arm Description

Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).

Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.

Outcomes

Primary Outcome Measures

Immune response
Summarized using means and confidence intervals (after transformation to render the data compatible with the assumptions of the normal distribution).
Immune response
Summarized using means and confidence intervals (after transformation to render the data compatible with the assumptions of the normal distribution).

Secondary Outcome Measures

Disease-free survival
Kaplan-Meier curves will be drawn to display the survival and time to recurrence. The log-rank test and estimates of relative risk based on the log-rank statistics will be performed. 95% confidence intervals will be constructed for the median DFS and OS.
Overall survival
Kaplan-Meier curves will be drawn to display the survival and time to recurrence. The log-rank test and estimates of relative risk based on the log-rank statistics will be performed. 95% confidence intervals will be constructed for the median DFS and OS.

Full Information

First Posted
August 4, 2004
Last Updated
April 14, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00089063
Brief Title
Vaccine Therapy With or Without Sargramostim in Treating Patients Who Have Undergone Surgery for Melanoma
Official Title
A Randomized Phase II Continuation Booster Trial After A Vaccine Combining Tyrosinase/GP100/Mart-1 Peptides Emulsified With Montanide ISA 51 and ISA 51 VG With Or Without GM-CSF For Patients With Resected Stages IIB/C, III And IV Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
June 2004 (undefined)
Primary Completion Date
June 2007 (Actual)
Study Completion Date
June 2007 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
This randomized phase II trial is studying vaccine therapy and sargramostim to see how well they work compared to vaccine therapy alone in treating patients who have undergone surgery for stage IIB, stage IIC, stage III, or stage IV melanoma. Vaccines made from peptides may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may make a stronger immune response.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate immune reactivity to a tyrosinase:368-376 (370D) /gp100: 209-217 (210M)/MART-1 26-35 (27L) peptide vaccine with Montanide ISA 51 with or without GM-CSF administered as a booster for five vaccinations over two years. OUTLINE: This is a randomized, parallel, continuation study. Patients are stratified according to response to prior vaccination (response to 1 peptide vs response to 2 or more peptides). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG subcutaneously (SC) on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations). Arm II: Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed at 2-4 weeks, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 40 patients (20 per treatment arm) will be accrued for this study within 1 year.

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, Extraocular Extension Melanoma, Iris Melanoma, Stage IIB Melanoma, Stage IIC Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Arm I (vaccine therapy)
Arm Type
Experimental
Arm Description
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG SC on day 1 of weeks 0, 26, 52, 78, and 104 (total of 5 vaccinations).
Arm Title
Arm II (vaccine therapy, sargramostim)
Arm Type
Experimental
Arm Description
Patients receive vaccination comprising tyrosinase peptide, gp100 antigen, and MART-1 antigen emulsified with Montanide ISA-51 and ISA-51 VG as in arm I. Patients also receive sargramostim (GM-CSF) SC on days 1-5 of weeks 0, 26, 52, 78, and 104.
Intervention Type
Biological
Intervention Name(s)
tyrosinase peptide
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
gp100 antigen
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
MART-1 antigen
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
incomplete Freund's adjuvant
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Montanide ISA 51 VG
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
sargramostim
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Immune response
Description
Summarized using means and confidence intervals (after transformation to render the data compatible with the assumptions of the normal distribution).
Time Frame
Baseline
Title
Immune response
Description
Summarized using means and confidence intervals (after transformation to render the data compatible with the assumptions of the normal distribution).
Time Frame
Week 106
Secondary Outcome Measure Information:
Title
Disease-free survival
Description
Kaplan-Meier curves will be drawn to display the survival and time to recurrence. The log-rank test and estimates of relative risk based on the log-rank statistics will be performed. 95% confidence intervals will be constructed for the median DFS and OS.
Time Frame
Up to 2 years
Title
Overall survival
Description
Kaplan-Meier curves will be drawn to display the survival and time to recurrence. The log-rank test and estimates of relative risk based on the log-rank statistics will be performed. 95% confidence intervals will be constructed for the median DFS and OS.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who have completed protocol 10M-01-1 or 10M-00-4 are eligible for this study provided that They have received all injections with evidence of an immune response They have not experienced recurrence of the melanoma Not more than twelve months have elapsed since the final injection on either protocol They experienced no grade 3 or 4 toxicity attributed to the prior vaccine regimen Serum creatinine of 2.0 mg/dl or less Total bilirubin of 2.0 mg/dl or less SGOT/SGPT of 2.5 X institutional norm or less Total WBC of 3,000 or more At least 1500 granulocytes Hemoglobin of 9.0 gm/dl or more Platelet count of 100,000 per cu mm. or more 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 IRB-approved informed consent Patients who have had another malignancy but with no evidence of disease for greater than 5 years from accrual to the current trial will be eligible if it is felt they are likely to be cured; patients with squamous or basal carcinoma of the skin or carcinoma in situ of the cervix that have been treated with curative intent can be accrued to this trial 30 days after treatment Exclusion Criteria: Who have undergone any other systemic therapy for their melanoma, including radiation therapy since completion of 10M-01-1 or 10M-00-4 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 systemic, ocular or inhaled corticosteroids Who are pregnant or lactating, since the risk of autoimmune reactivity to tyrosinase, MART-1 or gp100 is felt to present a risk to the fetus or a breast feeding infant; effective birth control for men and women is required during and for four months after the study is finished Who are known to be positive for hepatitis BsAg, hepatitis C antibody or HIV antibody; since cells removed for ex vivo handling and tissue culture cannot be virus positive, and the effects of melanoma peptides 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 GM-CSF, Montanide ISA 51 (IFA) or any of the peptides included in this protocol Who have a prior history of uveitis or autoimmune inflammatory eye disease, immune hemolytic anemia or other active autoimmune disease
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

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Vaccine Therapy With or Without Sargramostim in Treating Patients Who Have Undergone Surgery for Melanoma

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