Melanoma (Skin)
Conditions
Keywords
stage II melanoma, stage III melanoma, stage IV melanoma, recurrent melanoma
Brief summary
RATIONALE: Vaccines made from peptide 946 may make the body build an immune response to kill tumor cells. Combining these vaccines with proteins from the tetanus vaccine, and/or with either QS21 or Montanide ISA-51 may be an effective treatment for metastatic melanoma. PURPOSE: Randomized phase I trial to study the effectiveness of vaccines made from peptide 946 with or without tetanus peptide, QS21, or Montanide ISA-51 in treating patients with metastatic melanoma that cannot be surgically removed or with melanoma that is likely to recur.
Detailed description
OBJECTIVES: I. Determine the safety of peptide 946 melanoma vaccine (peptide 946), peptide 946 combined with tetanus peptide melanoma vaccine, or peptide 946-tetanus peptide conjugate in patients with high risk melanoma. II. Determine the immunogenicity of peptide 946 melanoma vaccine (peptide 946), peptide 946 combined with tetanus peptide melanoma vaccine, or peptide 946-tetanus peptide conjugate in patients with high risk melanoma. OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 6 treatment arms: Arm I: Patients receive peptide 946 melanoma vaccine (peptide 946) emulsified with QS21 subcutaneously (SQ). Arm II: Patients receive peptide 946 emulsified with Montanide ISA-51 (ISA-51) SQ. Arm III: Patients receive peptide 946 combined with tetanus peptide melanoma vaccine (tetanus peptide) emulsified with QS21 SQ. Arm IV: Patients receive peptide 946 combined with tetanus peptide emulsified with ISA-51 SQ. Arm V: Patients receive peptide 946-tetanus peptide conjugate emulsified with QS21 SQ. Arm VI: Patients receive peptide 946-tetanus peptide conjugate emulsified with ISA-51 SQ. Initially, 4 patients are randomized to Arm I and 4 patients are randomized to Arm II. If no dose limiting toxicities are observed in these patients, then additional patients are randomized to arms III-VI. Patients in each arm receive vaccine on day 0 and at months 1, 2, 3, 6, 9, and 12. Patients are followed at 6 and 12 months. PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study.
Interventions
BIOLOGICALQS21
vaccine adjuvant
BIOLOGICALIFA (incomplete Freund's adjuvant)
Peptides emulsified in IFA.
BIOLOGICALp946
This a nonamer peptide YLEPGPVTA from Gp100, used as a melanoma vaccine antigen.
BIOLOGICALp946/tet-p
This peptide is a longer version of p946 (gp100 \[280-288\]) sythesized colinearly with the tetanus helper peptide (Tet-p)
BIOLOGICALTet-p
modified form of the p2 peptide from tetanus toxoid, used as nonspecific epitope for helper T cells.
Sponsors
National Cancer Institute (NCI)
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed unresectable metastatic melanoma (AJCC stage III or IV) OR resected melanoma with high risk of recurrence or mortality (stage IIB and above) * Age: 18 to 79 * Performance status: ECOG 0-2 * Life expectancy: Greater than 12 months * Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL * Hepatic: AST and ALT no greater than 2.5 times upper limit of normal (ULN) Bilirubin no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN * Renal: Creatinine no greater than 1.5 times ULN
Exclusion criteria
* patients currently receiving cytotoxic chemotherapy or who have received that therapy within the preceding 3 months * known or suspected allergies to any component of the treatment vaccine * unresectable tumor llikely to cause symptoms and for which therapy is anticipated within 3 months. * receiving acute treatment for seriouis infection within 14 days. * Patients with bulky disease, or with multiple brain metastases, but solitary brain metastases treated successfully with surgery or gamma knife may be eligible. * Any of the following with 3 months: * agentes with putative immunomodulating activity (except NSAIDs) * allergy desensitizing injections * other investigational agents * interferons * corticosteroids * any growth factors * prior melanoma vaccinations * pregnancy or the possibility of becoming pregnant on study * medical contraindication or potential problems in complying with the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Grade 3 Adverse Events | Up to 24 months after last vaccine | Adverse events are monitored according to NCI/DCT Common Toxicity Criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of Each Vaccine Regimen | up to 12 months since enrollment | T cell responses to the p946 (gp100 \[280-288\]) peptide. All enrolled patients were assayed for immune response to the gp100 peptide by ELIspot assay after 14 days in vitro sensitization. The number with a response in each study arm is reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Proliferative Response to Tetanus Helper Peptide | during vaccination | Proliferative response measured in participants using a tritiated thymidine incorporation assay with peripheral blood mononuclear cells (PBMC) stimulated with the tetanus peptide in vitro, and measured at 5 days after in vitro culture. |
Countries
United States
Participant flow
Recruitment details
patients were enrolled at the University of Virginia
Pre-assignment details
no enrolled patients were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Peptide 946 Plus QS-21 100 mcg peptide gp100 \[280-288\] plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant | 4 |
| Group 2. p946 Plus IFA 100 mcg peptide gp100 \[280-288\] plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant | 5 |
| Group 3: p946 Plus Tet-p Plus QS-21 100 mcg peptide gp100 \[280-288\],190 mcg tetanus peptide, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant | 4 |
| Group 4. p946, Tet-p Plus IFA 100 mcg peptide gp100 \[280-288\], 190 mcg tetanus peptide, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant | 2 |
| Group 5: p946/Tet-p Plus QS-21 282 mcg gp100 \[280-288\]/tetanus peptide conjugate, plus 0.2 ml (100 mcg) QS-21 vaccine adjuvant | 4 |
| Group 6. p946/Tet-p Plus IFA 282 mcg gp100 \[280-288\]/tetanus peptide conjugate, plus 0.5 ml IFA (Montanide ISA-51) vaccine adjuvant | 3 |
| Total | 22 |
Baseline characteristics
| Characteristic | Group 2. p946 Plus IFA | Group 3: p946 Plus Tet-p Plus QS-21 | Group 4. p946, Tet-p Plus IFA | Group 1: Peptide 946 Plus QS-21 | Group 5: p946/Tet-p Plus QS-21 | Group 6. p946/Tet-p Plus IFA | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 14 Participants |
| Age, Continuous | 59.6 years STANDARD_DEVIATION 18.6 | 44.3 years STANDARD_DEVIATION 16.8 | 59.5 years STANDARD_DEVIATION 17.7 | 53.8 years STANDARD_DEVIATION 17.1 | 51.8 years STANDARD_DEVIATION 14.9 | 69.3 years STANDARD_DEVIATION 7.5 | 55.6 years STANDARD_DEVIATION 16.1 |
| Region of Enrollment United States | 5 participants | 4 participants | 2 participants | 4 participants | 4 participants | 3 participants | 22 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 12 | 4 / 10 |
| serious Total, serious adverse events | 1 / 12 | 0 / 10 |
Outcome results
Primary
Safety: Grade 3 Adverse Events
Adverse events are monitored according to NCI/DCT Common Toxicity Criteria
Time frame: Up to 24 months after last vaccine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All QS-21 | Safety: Grade 3 Adverse Events | 1 participants |
| All Montanide ISA-51 | Safety: Grade 3 Adverse Events | 0 participants |
Secondary
Immunogenicity of Each Vaccine Regimen
T cell responses to the p946 (gp100 \[280-288\]) peptide. All enrolled patients were assayed for immune response to the gp100 peptide by ELIspot assay after 14 days in vitro sensitization. The number with a response in each study arm is reported.
Time frame: up to 12 months since enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All QS-21 | Immunogenicity of Each Vaccine Regimen | 1 participants |
| All Montanide ISA-51 | Immunogenicity of Each Vaccine Regimen | 1 participants |
| Group 3: p946 Plus Tet-p Plus QS-21 | Immunogenicity of Each Vaccine Regimen | 0 participants |
| Group 4. p946, Tet-p Plus IFA | Immunogenicity of Each Vaccine Regimen | 1 participants |
| Group 5: p946/Tet-p Plus QS-21 | Immunogenicity of Each Vaccine Regimen | 0 participants |
| Group 6. p946/Tet-p Plus IFA | Immunogenicity of Each Vaccine Regimen | 0 participants |
Other Pre-specified
Number of Participants With a Proliferative Response to Tetanus Helper Peptide
Proliferative response measured in participants using a tritiated thymidine incorporation assay with peripheral blood mononuclear cells (PBMC) stimulated with the tetanus peptide in vitro, and measured at 5 days after in vitro culture.
Time frame: during vaccination
Population: All evaluable enrolled patients were assayed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All QS-21 | Number of Participants With a Proliferative Response to Tetanus Helper Peptide | 1 participants |
| All Montanide ISA-51 | Number of Participants With a Proliferative Response to Tetanus Helper Peptide | 0 participants |
| Group 3: p946 Plus Tet-p Plus QS-21 | Number of Participants With a Proliferative Response to Tetanus Helper Peptide | 1 participants |
| Group 4. p946, Tet-p Plus IFA | Number of Participants With a Proliferative Response to Tetanus Helper Peptide | 2 participants |
| Group 5: p946/Tet-p Plus QS-21 | Number of Participants With a Proliferative Response to Tetanus Helper Peptide | 4 participants |
| Group 6. p946/Tet-p Plus IFA | Number of Participants With a Proliferative Response to Tetanus Helper Peptide | 2 participants |