Utility of Novel BRAF Test for Melanoma

NCT01840527 | Completed Results

• 2 other identifiers: 12-4881UH2CA207355
• Study Type: observational
• Target: 220
• Locations: 1 country
• Sites: 3

Brief Summary

This primary purpose of this study is to obtain blood samples from participants with both early and later stages of melanoma (Stage II/III and Stage IV). The researchers hope to better understand an abnormal protein found in many melanoma tumors called the BRAFV600 mutation. There will be two separate cohorts (groups) of participants on this study. You will be placed in one of the Groups. Group 1-For participants with advanced melanoma: Your existing tumor tissue sample will be compared to the blood samples given in order to further analyze and to understand the BRAFV600E gene mutation. Group 2-For participants with stage II/III melanoma: Following surgery, blood samples will be collected and analyzed. Understanding the BRAFV600E gene mutation in melanoma will help the researchers better understand the disease, and help plan treatment options for people with melanoma of all stages in the future.

Conditions

Melanoma

Keywords

Biomarker; BRAF; blood-based

Outcome Measures

Primary Outcomes (2)

• Determine Sensitivity of Blood-Based Assay

  The specificity and sensitivity of the blood-based assay will be determined vis-à-vis tissue-based BRAF analysis in patients with advanced and high-risk melanoma in order to provide BRAF-directed therapy when indicated. The sensitivity of an assay is expressed as the probability (as a percentage) that a sample tests positive for BRAF mutation given that the participant has BRAF mutation; it is used to assess the risk of false negative results. A percentage greater than 50% indicates that the test is a better predictor of sample diagnosis than random chance.

  2 years

• Determine Specificity of Blood-Based Assay

  The specificity and sensitivity of the blood-based assay will be determined vis-à-vis tissue-based BRAF analysis in patients with advanced and high-risk melanoma in order to provide BRAF-directed therapy when indicated. The specificity of an assay is expressed as the probability (as a percentage) that a test returns a negative result for BRAF mutation given that the that participant does not BRAF mutation; it is used to assess the risk of false positive results. A percentage greater than 50% indicates that the test is a better predictor of sample diagnosis than random chance.

  2 years

Secondary Outcomes (2)

• Explore Pharmacodynamic Effects of MAPK Pathway Inhibitors

  2 years

• Define Prognostic Value of Peripheral Blood BRAFV600 Testing in Melanoma

  2 years

Study Arms (2)

Advanced Melanoma

For patients in the advanced melanoma cohort, a one-time blood sample will be obtained prior to the commencement of systemic therapy at a time when standard-of-care blood will be drawn. While it is ideal to obtain samples prior to any systemic therapy, participants who have previously received therapy, have progressed, and are in need of additional therapy will be considered suitable for participation. Participants with known BRAF mutation (determined by standard of care tissue testing) will undergo blood draws every 4 weeks (+/- 1 week) and at the time of disease progression.

Stage II/III Melanoma

For patients in the high-risk stage II/III cohort, a blood draw will be performed 4-8 weeks after the completion of surgical management at the time of standard of care blood work. In participants who sign informed consent prior to definite surgical management, a pre-operative blood draw may be obtained at the time that standard of care pre-op blood work is performed. Blood samples will then be obtained every three months following the initiation of either adjuvant therapy or routine, close follow-up for up to two years.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients being treated at Massachusetts General Hospital, Dana-Farber Cancer Institute and Beth Isreal Deaconess Medical Center

You may qualify if:

• Biopsy proven advanced (unresectable stage IIIC or stage IV)or high risk (stage II or stage III) malignant melanoma

You may not qualify if:

• History of a different malignancy except for the following circumstances: disease-free for at least 2 years and deemed by the investigator to be at low risk for recurrence; or non-metastatic prostate cancer, cervical cancer in situ and basal cell or squamous cell carcinoma
• Known history of a different BRAF mutant malignancy

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood lymphocytes (PBLs); Plasma; Tumor Tissue

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The study's primary outcome was not reached because the assay has not been successfully developed so no collected samples could be analyzed. More sensitive ctDNA approaches have made their way into commercial use including bespoke assays during the course of this study. The value of a highly-sensitive BRAF specific assay seemed less useful, and given the past troubles developing the current assay approach, the study team decided to apply the philanthropic funds to other projects.

Results Point of Contact

• Title: Ryan Sullivan
• Organization: Massachusetts General Hospital Cancer Center

rsullivan7@mgh.harvard.edu

6177244000

Study Officials

• Ryan Sullivan, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 25, 2013
• Study Start: May 1, 2013
• Primary Completion: March 29, 2017
• Study Completion: September 1, 2022
• Last Updated: September 4, 2024
• Results First Posted: September 4, 2024

Record last verified: 2024-08

Locations

US (3)