Prognostic Gene Expression Profiling and Adjuvant Therapy in Stage IIIA-B Cutaneous Melanoma (PERSONALize)

Cutaneous melanoma (CM) is a common skin cancer with more than 75,000 cases diagnosed in the Unites States each year. When participants are diagnosed with CM, the characteristics of their tumor, such as Breslow thickness (thickness of tumor measured in millimeters), are looked at to determine the risk of the skin cancer spreading to other parts of the body, such as the lymph nodes. Lymph nodes are part of the immune system and are found throughout the body. The presence of cancer in the lymph node to which cancer is most likely to spread first, or sentinel lymph node (SLN), is one of the most important ways to learn of the risk of the cancer spreading.

A surgical procedure called a sentinel lymph node biopsy (SLNB) is performed to learn if there is cancer in the SLN. The SLNB procedure itself does not increase survival.

When the cancer is found in the SLN, it is considered to be Stage III. National guidelines for the treatment of Stage III melanoma recommend frequent office visits and the use of laboratory tests and imaging to help find metastases as soon as possible and treat them. Medications such as immunotherapy and targeted therapy after surgery have been studied and are currently being used to treat this type of cancer. Ipilimumab, nivolumab, and pembrolizumab, are FDA-approved medications used for this type of cancer.

Given the side effects that can happen with cancer medications, it is important to be able to predict which Stage III melanoma patients are at high-risk for their disease spreading and may really benefit from additional medications. For patients at a low risk for the cancer spreading, it is also important to know whether the benefit from the medication outweighs the risks.

The DecisionDx®-Melanoma gene expression assay (test) was developed to determine the risk of metastasis (spread of disease) in early stage melanoma participants. DecisionDx®-Melanoma puts patients into low risk (Class 1A), intermediate (Class 1B, 2A) or high risk (Class 2B) groups for developing metastasis within five years of the diagnosis of melanoma.

As the DecisionDx®-Melanoma test has been shown to be able to identify Stage III patients with low and high risks of their cancer spreading, it could also help predict which patients are less likely to benefit from therapy after surgery and may only need to be watched more closely with visits to your doctors’ office and imaging scans like CTs or PET scans. It may also help find high-risk patients who may benefit more from additional therapy. This study is being done to learn the outcomes of Stage IIIA-B patients and how it relates to DecisionDx®-Melanoma test results; as well as looking at the differences in how patients respond to medication treatment(s) between low-risk and high-risk classes.

Inova Schar Cancer Institute
8081 Innovation Park Dr.
Fairfax, VA 22031

A department of Inova Fairfax Hospital

• Adults, 18 years of age or older at the time of the cutaneous melanoma diagnosis
• Participant diagnosed after January 1, 2018, with Stage IIIA or Stage IIIB (AJCC 8th edition) cutaneous melanoma
• Nodal staging (i.e. sentinel lymph node biopsy) was completed within 4 months of diagnosis of cutaneous melanoma
• If participant received adjuvant therapy, it was a PD-1 or CTLA-4 inhibitor (i.e. pembrolizumab, nivolumab, ipilimumab) or targeted therapy (i.e. dabrafenib/trametinib or other similar targeted therapies)
• Additional eligibility in protocol.

• Participant with Stage I/II cutaneous melanoma at diagnosis, who subsequently developed Stage III disease more than 4 months after their original diagnosis, or nodal staging (i.e. sentinel lymph node biopsy) was performed more than 4 months after diagnosis.
• Participant who had Stage IIIC or IIID melanoma (by AJCC v8) at diagnosis, which includes one of the following:
  
  Primary tumor with Breslow thickness of greater than 2.0 mm to 4.0 mm with ulceration (T3b)
  OR
  Primary tumor with Breslow thickness greater than 4.0 mm with or without ulceration (T4a or T4b)
  OR
  Tumor-involved regional lymph nodes concurrent with in-transit, satellites, or microsatellite metastases (N2c or N3c)
  OR
  Four or more tumor-involved regional lymph nodes (N3a or N3b).
   
• Participant for whom clinical testing with DecisionDx®-Melanoma is not appropriate (i.e.: in situ melanoma, stage IV disease at time of diagnosis, any other non-eligible clinical population).
• Participant who received adjuvant interferon therapy for treatment of their melanoma.
• Participant with a current diagnosis of any other invasive cancer, with the exception of the following:
  • Basal cell carcinoma or cutaneous squamous cell carcinoma considered to be cured by the Investigator
  • Invasive breast cancer and prostate cancer diagnosed more than 5 years prior to diagnosis of cutaneous melanoma if no progression of disease is noted.
• Additional ineligibility in protocol.