Recurrent Melanoma, Stage IA Melanoma, Stage IB Melanoma, Stage IIA Melanoma, Stage IIB Melanoma, Stage IIC Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma
Conditions
Brief summary
This randomized pilot phase II trial studies how well vaccine therapy works in treating human leukocyte antigen class 1 histocompatibility, A-2 (HLA-A2) positive patients with melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217\[210M\] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma \> 1 mm thick. II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide. III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20. IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide tetramers is an effective method for monitoring the immune response of patients undergoing peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT), limiting dilution analysis (LDA) and measurement of intracellular cytokine production (fastimmune). V. To determine whether there is a difference between the induction of primary peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7 peptide. VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant subcutaneously (SC) every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. In both arms, patients undergo sentinel lymph node biopsy approximately 10 days after the second vaccination. Patients with positive lymph nodes undergo complete lymph node dissection and resume vaccinations. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.
Interventions
BIOLOGICALHPV 16 E7:12-20
Given SC
BIOLOGICALgp100:209-217(210M)
Given SC
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed primary melanoma of Breslow thickness 1.0-4.0 mm; patients who have had only their initial biopsy are preferred; however, those who have already undergone a wide local excision are also eligible; patients may be enrolled up to three months after their wide local excision * Patients whose melanoma is \> 4.0 mm thick who have positive or negative regional lymph nodes are also eligible * After accrual to the original 26 patient goal, all patients must be enrolled prior to sentinel lymph node dissection; patients with previous lymph node dissection will not be eligible * Patients must be HLA typed and be shown to be HLA-A2.1+ by either serologic techniques, flow cytometry, or molecular techniques * Patients must be ambulatory with good performance status (Karnofsky performance status \[PS\] 80-100) * White blood cell (WBC) \>= 3500/mm\^3 * Platelets (Plt) \>= 100,000/mm\^3 * Hemoglobin \>= 9 gm/100 ml * Serum creatinine =\< 2 mg/dl * Total bilirubin =\< 2.0 mg/dl * Patients must have recovered from any effects of major surgery and be free of significant systemic infection * Patients must be negative for human immunodeficiency virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) (or negative by Western blot if ELISA is positive) if they are considered to be at high risk; others do not require serologic testing if there are no symptoms or risk factors for HIV disease * Women of childbearing potential must have a negative pregnancy test and should avoid becoming pregnant while on treatment * Patients must give written informed consent prior to initiation of therapy; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy
Exclusion criteria
* Patients must not have clinically detectable distant metastases * Patients who require or are likely to require systemic corticosteroids for intercurrent illness * Patients with any significant medical disease other than the malignancy (e.g. chronic obstructive pulmonary disorder \[COPD\], patients with ascites or pleural effusions) which in the opinion of the investigator would significantly increase the risk of immunotherapy * Patient should be free of any other cancers or deemed at low risk for their recurrence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | Baseline to 6 months | Frequency measures obtained from each assay will be transformed to (common) logs for purposes of analysis. Repeated measures analyses will be performed on longitudinal data to assess patients' immune response profiles over time. Comparability of assay methods will be assessed with correlation analyses, regression analyses, standard parametric and nonparametric tests, and agreement methods. Pre- and post-immunization T-cell immunity to g209-2M peptide, to HPV16E7 peptide, and to a negative control HLA-A2 HIV peptide (pol) were assessed using HLA-A2/peptide tetramer-specific binding analysis. Within-subject analyses were performed to determine differences between pre- and postimmunization responses to the g209 -2M and HPV peptides and to the negative control HIV peptide after completion of 6 months of vaccination. Pre- versus postimmunization response differences were used as criterion measures in between-group (among subjects) analyses. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A (Every 2 Weeks) | 18 |
| Arm B (Every 3 Weeks) | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Patient Vacation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Arm A (Every 2 Weeks) | Arm B (Every 3 Weeks) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 14 Participants | 28 Participants |
| Gender Female | 7 Participants | 9 Participants | 16 Participants |
| Gender Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 18 | 17 / 18 |
| serious Total, serious adverse events | 1 / 18 | 0 / 18 |
Outcome results
Primary
T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide
Frequency measures obtained from each assay will be transformed to (common) logs for purposes of analysis. Repeated measures analyses will be performed on longitudinal data to assess patients' immune response profiles over time. Comparability of assay methods will be assessed with correlation analyses, regression analyses, standard parametric and nonparametric tests, and agreement methods. Pre- and post-immunization T-cell immunity to g209-2M peptide, to HPV16E7 peptide, and to a negative control HLA-A2 HIV peptide (pol) were assessed using HLA-A2/peptide tetramer-specific binding analysis. Within-subject analyses were performed to determine differences between pre- and postimmunization responses to the g209 -2M and HPV peptides and to the negative control HIV peptide after completion of 6 months of vaccination. Pre- versus postimmunization response differences were used as criterion measures in between-group (among subjects) analyses.
Time frame: Baseline to 6 months
Population: Patients were randomly assigned to two different vaccination schedules: group A received vaccinations every 2 weeks for 6 months (13 total injections), and group B received vaccinations every 3 weeks for 6 months (nine total vaccinations).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | Post-treatment % gp100 g209-2M-specific T cells | 0.97 % of CD8+ T cells |
| Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | Pre-Treatment % HPV16:E7 12-20-specific T cells | 0.61 % of CD8+ T cells |
| Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | Post-Treatment % HPV16:E7 12-20-specific T cells | 0.68 % of CD8+ T cells |
| Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | pre-treatment %gp100 g209-2M-specific T cells | 0.02 % of CD8+ T cells |
| Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | pre-treatment %gp100 g209-2M-specific T cells | 0.01 % of CD8+ T cells |
| Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | Post-treatment % gp100 g209-2M-specific T cells | 0.98 % of CD8+ T cells |
| Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | Post-Treatment % HPV16:E7 12-20-specific T cells | 1.34 % of CD8+ T cells |
| Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20) | T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide | Pre-Treatment % HPV16:E7 12-20-specific T cells | 0.1 % of CD8+ T cells |
p-value: <0.001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
p-value: 0.59t-test, 2 sided