Breakthrough Clinical Trial Results
for Melanoma

A recent clinical trial-led by Goshen Center for Cancer Care-has yielded promising results for metastatic
melanoma treatment and the future use of a cancer vaccine. For the first time ever, the new cancer vaccine doubled the response rate for tumor shrinkage as well as delayed the progression of cancer in patients with metastatic melanoma.

Providing hope that we are making progress, this is one of the first studies-and the first step-to prove vaccines might have a medical benefit against cancer. Goshen's not-for-profit status has enabled us to pursue this
study, along with other quality research initiatives and clinical trials that will move us forward in the treatment
of all cancers.

Goshen acted as the coordinating center, and the only site in Indiana, for this multi-institute, national clinical trial. As the lead author and principle investigator, Goshen Center for Cancer Care Medical Director Dr. Doug Schwartzentruber brought his melanoma expertise and the clinical trial to Goshen five years ago from the National Cancer Institute (NCI).

The eight-year NCI trial tested the effectiveness of combining the vaccine with the metastatic melanoma therapy high-dose Interleukin-2 (IL-2). Involving 21 sites and 185 patients, the study investigated whether IL-2 given with the vaccine would create positive responses for more patients, making the body's immune response even stronger than with IL-2 alone.

How It Works

Both IL-2 and the cancer vaccine are considered biologic therapies, meaning they help a patient's own immune system fight the cancer. Other treatments, such as chemotherapy, attack cancer cells directly-while also damaging healthy tissue and often causing undesirable side effects. The clinical trial results also lend support for successfully combining other biologic treatments.

Typically, vaccines are meant to help the immune system fight off something foreign, like preventing an infection. Cancer vaccines differ from other vaccines because they work on the disease after it's already established in the body. The vaccine used in this cancer trial is a synthetic fragment from a specific protein found on the surface of melanoma cells. This protein, the gp100 protein, acts as a marker to help identify melanoma cells. The vaccine primes a patient's immune system to find and attack the cancer by locating the gp100 protein.

The other half of the biologic combination is high-dose IL-2, an approved treatment for metastatic melanoma, that causes very good responses in a limited number of patients. Goshen is one of only 60 specialized centers in the United States with the training and expertise to offer the therapy. The genetically engineered IL-2 enhances natural compounds already produced in the body to boost the immune system.

Combining the cancer vaccine with IL-2 maximizes the effect of using IL-2 alone. IL-2 can be thought of as a "growth factor" that activates more white blood cells. The vaccine then uses this greater immune response to more effectively find and attack the melanoma cells by locating the specific protein.

The Breakthrough Results

Metastatic melanoma is a very difficult cancer to treat successfully because it is resistant to most drugs. The trial proved that the vaccine enhanced the effect of IL-2 by doubling the number of people who had a positive response and delaying the progression of the cancer. The study also showed a trend toward overall survival.

According to Schwartzentruber, these results give patients and the oncology community hope that we are making progress against the disease. Before the vaccine could be introduced as treatment for melanoma, the next step would be to conduct a larger clinical trial to show the vaccine does indeed improve overall survival.

Schwartzentruber also emphasized that cancer progress is made one step at a time, with clinical trials contributing to major medical breakthroughs. Goshen Center for Cancer Care continues to be committed to cancer research-involved in and sponsoring a number of clinical trials involving prevention, screening, diagnostics, treatment and quality of life. Through these various types of trials, research is conducted with the participation of patients on a voluntary basis. Goshen Center for Cancer Care actively engages in collaborations with other cancer centers and academic institutions to further progress research.

The Clinical Trial Outline

A Phase III Multi-Institutional Randomized Study of Immunization w/gp100: 209-217(210M) Peptide Followed by High Dose IL-2 vs. High Dose IL-2 Alone In Patients with Metastatic Melanoma

Goshen Center for Cancer Care was the coordinating center for this multi-institutional trial that recently closed to accrual. Eligible patients were those with locally advanced stage III or IV metastatic melanoma as well as tissue type HLA-A0201 positive.

IL-2 stimulates the proliferation of lymphocytes, which results in the destruction of cancer cells. Vaccines may help make the immune response stronger. The purpose of this randomized phase III trial was to compare the effectiveness of IL-2 with or without vaccine therapy in treating patients with metastatic melanoma.

There were 185 patients who were randomly selected to participate in one of the two treatment arms:
-Arm I: Patients received IL-2 only.
-Arm II: Patients received gp100 antigen emulsified in Montanide ISA-51 subcutaneously in addition to IL-2.

The primary outcome measure was clinical response. Secondary outcome measures included disease free and progression free survival rates, toxicity, immunologic response and quality of life before and after the first course of treatment.

The following preliminary results were presented at the annual meeting of the American Society of Clinical Oncology in May 2009:
-Doubled the response rate for tumor shrinkage.
-Extended progression free survival
-Trend towards improvement in overall survival