Melanoma
Conditions
Keywords
Biomarker, BRAF, blood-based
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.
Detailed description
There will be no extra clinic visits for this study. These research blood samples will be drawn at the same time as your regularly scheduled blood draws that are part of standard care for melanoma. About 2 to 4 teaspoons of blood will be drawn for each research sample. Depending on which group you are in, you will have either a one time blood draw or ongoing blood work for 1-2 years.
Interventions
None listed
Sponsors
Massachusetts General Hospital
National Cancer Institute (NCI)
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy proven advanced (unresectable stage IIIC or stage IV)or high risk (stage II or stage III) malignant melanoma
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Sensitivity of Blood-Based Assay | 2 years | 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. |
| Determine Specificity of Blood-Based Assay | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Explore Pharmacodynamic Effects of MAPK Pathway Inhibitors | 2 years | To explore the pharmacodynamic effects of MAPK pathway inhibitors (including selective BRAF inhibitors, MEK inhibitors, and ERK inhibitors) utilizing pre-and on-treatment peripheral blood BRAFV600E mutational testing in participants with advanced melanoma. |
| Define Prognostic Value of Peripheral Blood BRAFV600 Testing in Melanoma | 2 years | To define the prognostic value of peripheral blood BRAFV600 mutational testing in participants with Stage II/III melanoma |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRyan Sullivan, MD
Massachusetts General Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 110 |
| 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. | 110 |
| Total | 220 |
Baseline characteristics
| Characteristic | Advanced Melanoma | Total | Stage II/III Melanoma |
|---|---|---|---|
| Age, Continuous | 59.8 years | 59.7 years | 59.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 101 Participants | 202 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 17 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) White | 105 Participants | 210 Participants | 105 Participants |
| Region of Enrollment United States | 110 participants | 220 participants | 110 participants |
| Sex: Female, Male Female | 33 Participants | 65 Participants | 32 Participants |
| Sex: Female, Male Male | 77 Participants | 155 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 68 / 110 | 40 / 110 |
| other Total, other adverse events | 0 / 110 | 0 / 110 |
| serious Total, serious adverse events | 0 / 110 | 0 / 110 |
Outcome results
Primary
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.
Time frame: 2 years
Population: 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.
Primary
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.
Time frame: 2 years
Population: 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.
Secondary
Define Prognostic Value of Peripheral Blood BRAFV600 Testing in Melanoma
To define the prognostic value of peripheral blood BRAFV600 mutational testing in participants with Stage II/III melanoma
Time frame: 2 years
Population: 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.
Secondary
Explore Pharmacodynamic Effects of MAPK Pathway Inhibitors
To explore the pharmacodynamic effects of MAPK pathway inhibitors (including selective BRAF inhibitors, MEK inhibitors, and ERK inhibitors) utilizing pre-and on-treatment peripheral blood BRAFV600E mutational testing in participants with advanced melanoma.
Time frame: 2 years
Population: 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.