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Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High Risk Melanoma


Phase 2
7 Years
N/A
Not Enrolling
Both
High-Risk Melanoma

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Trial Information

Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High Risk Melanoma


Background:

A previous clinical trial has been conducted in the Surgery Branch National Cancer Institute
(NCI) in which gp100 immunizations have been administered to patients with melanoma in the
adjuvant setting. In this prior protocol, the peptide emulsified in Incomplete Freund's
Adjuvant was administered subcutaneously using several different schedules and was well
tolerated except for mild and transient erythema at the site of injection. Each of the
schedules provided successful immunization although the q3w schedule was the best tolerated
locally and three courses of immunization appeared to be sufficient using this regimen. An
important finding from the adjuvant protocol however was the significant increase in immune
precursors specifically reactive against peptide and tumor that occurred with increasing
courses of immunization. These findings have encouraged us to now further explore the
optimal methods for generating immune precursors using the gp100:209-217(210M) peptide by
testing the impact of an additional immune adjuvant, imiquimod, reported to increase the
immunizing potential of antigens as well as evaluate an alternate route of injection,
intradermal administration.

Objectives:

The primary objective of this trial is to evaluate the immunologic activity of immunization
with four different preparations of the gp100:209-217(210M) melanoma antigen peptide and
potentially select one for further study.

Eligibility:

HLA-A 0201 patients, age greater than or equal 16 years, with primary melanomas with lesions
that are ulcerated and greater than or equal 2mm, or any lesions that are greater than or
equal 4.0 mm in thickness, or greater than or equal 1 positive lymph node, or local
recurrence, or resected metastatic disease, within 6 months of surgical resection will be
considered. Patients who have ocular or mucosal melanoma or who require systemic steroid
therapy will be excluded. The following patients will also be excluded: have previously
been immunized with gp100; have known hypersensitivity to any of the agents used in this
study; have previously received chemotherapy for treatment of melanoma; or who are
undergoing or have undergone in the past 3 weeks any systemic therapy except surgery for
their cancer.

Design:

Patients will be randomized into one of the following four arms:

1. gp100:209-217(210M) peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG
injected subcutaneously on day one every three weeks (1 cycle) for a total of twelve
cycles (33 weeks).

2. gp100:209-217(210M) peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG
injected subcutaneously on day one every three weeks (1 cycle) for a total of twelve
cycles (33 weeks); following the injection patients will apply imiquimod to the skin at
the site of injection daily for 5 days.

3. gp100:209-217(210M) in 0.9% Sodium Chloride Injection injected intradermally on day one
every three weeks (1 cycle) for a total of twelve cycles (33 weeks).

4. gp100:209-217(210M) peptide in 0.9% Sodium Chloride Injection injected intradermally on
day one every three weeks (1 cycle) for a total of twelve cycles (33 weeks); following
the injection patients will apply imiquimod to the skin at the site of the injection
daily for 5 days.

Immunizations will be administered on an outpatient basis unless side effects or the
patient's clinical condition warrants hospitalization. Patients will receive full clinical
evaluation three weeks after 8 cycles and 12 cycles.

Each of the arms will be conducted using a two-stage optimal design Since the primary
objective is to select one regimen from among the four on the basis of the immune response,
this design allows there to be greater than 80% probability of correctly selecting the
superior arm if there is either a tie in the number of immune responses, or if there is at
least one more immune response on one arm than the other three arms, and if the true
response rates are 15%, 15%, 15% and 35%. Initially, 19 patients will be enrolled in each
arm and evaluated; if 0 to 3 of 19 in an arm have an immune response to T2 cells pulsed with
0.01 M peptide after the 4th, 8th, and 12th cycles, no further patients would be randomized
to receive the peptide on that arm. If at least four immunologic responses are noted after
the 8th cycle, then accrual to 33 patients would take place. If all four arms need to be
completed and 33 patients need to be completed in each arm, a total of 132 patients are
required.

Inclusion Criteria


- INCLUSION CRITERIA:

HLA-A 0201 patients, age greater than or equal to 16 years, primary melanomas with lesions
that are ulcerated and greater than or equal to 2mm, or any lesions that are greater than
or equal to 4.0 mm in thickness, or greater than or equal to1 positive lymph node, or
local recurrence, or resected metastatic disease, within 6 months of surgical resection
will be considered. Patients must be clinically disease free at the time of protocol entry
as documented by radiologic studies within 6 weeks of patient entry.

Serum creatinine of 2.0 mg/dl or less

Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who must
have a total bilirubin less than 3.0 mg/dl.

WBC 3000/mm^3 or greater,

Platelet count 90,000 mm^3 or greater,

Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than three
times normal,

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients of both genders must be willing to practice effective birth control during this
trial because the potential for teratogenic effects are unknown.

Patients may have had prior adjuvant treatment with immunotherapy, including interferon,
as long as 3 weeks have elapsed since prior systemic therapy.

EXCLUSION CRITERIA:

Patients will be excluded:

Who have ocular or mucosal melanoma.

Who are undergoing or have undergone in the past 3 weeks any systemic therapy except
surgery for their cancer, and must have recovered to a grade I from any adverse effects of
treatment prior to entry, other than those that do not have clinical implications, e.g.
vitiligo, alopecia.

Have active systemic infections, autoimmune disease or any known immunodeficiency disease.

Who require systemic steroid therapy.

Who are pregnant (because of possible side effects on the fetus) or breastfeeding because
of unknown effects on the developing child).

Who are known to be positive for hepatitis BsAG or human immunodeficiency virus (HIV)
antibody (because of possible immune effects of these conditions).

Who have any form of autoimmune disease (such as autoimmune colitis or Crohn's Disease) or
immunodeficiency as evidenced by abnormal white blood count (WBC) count 8 and/or presence
of opportunistic infections. Must have recovered immune competence after radiation
therapy. (The experimental treatment being evaluated in this protocol depends on an intact
immune system. Patients who have decreased immune competence may be less responsive to the
experimental treatment and more susceptible to its toxicities.)

Who have previously been immunized with gp100.

Who have known hypersensitivity to any of the agents used in this study.

Who have previously received chemotherapy for treatment of melanoma.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Immunologic Response Rate

Outcome Description:

Comparison of six different preparations of the gp100:209-217 (210M) melanoma antigen peptide. The arm with the greater number of immunologic responses will be the one most likely to be selected for future study on the basis of immunization alone. Evidence of immunization consist of at least 10 Elispots/100,000 cells above background. An injection site reaction is not an immune response.

Outcome Time Frame:

48 months

Safety Issue:

No

Principal Investigator

Steven A Rosenberg, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health

Authority:

United States: Federal Government

Study ID:

060069

NCT ID:

NCT00273910

Start Date:

January 2006

Completion Date:

May 2010

Related Keywords:

  • High-Risk Melanoma
  • Disease Free Survival
  • gp 100:209-217 (210m)
  • Immunologic Response
  • Adjuvant Therapy
  • Cutaneous Melanoma
  • Melanoma
  • Melanoma

Name

Location

National Cancer Institute (NCI) Bethesda, Maryland  20892