Combined BRAF-Targeted Therapy & Immunotherapy for Melanoma
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2013 |
COMBAT 1: A Phase II Trial of Combined BRAF-Targeted Therapy and Immunotherapy for Melanoma
This research study is a Phase II clinical trial of an investigational combination of drugs
(vemurafenib and aldesleukin) to learn whether the combination works in treating a specific
cancer. While both vemurafenib and aldesleukin are approved by the FDA for the treatment of
metastatic melanoma, the FDA has not yet approved the combination of vemurafenib and
aldesleukin.
Researchers have found that a large number of melanoma cells have mutations in the BRAF
gene. It has been shown that vemurafenib blocks the effects of these mutations in the BRAF
gene, and, as a result, may help to prevent cancer growth.
Aldesleukin, also referred to as IL-2, is an immunotherapy drug administered via IV infusion
that increases the growth of key cells within the immune system that are responsible for
targeting cancer cells. Activating more of these key cells, called T-lymphocytes and
natural-killer cells, leads to increased cancer cell death.
The BRAF gene is located on a larger pathway called the MAPK pathway. Studies have shown
that when a BRAF inhibitor, like vemurafenib is used to block the MAPK pathway, melanocytes,
or cancer cells express more proteins on their surfaces, making them easier for
T-lymphocytes and natural killer cells to recognize and kill them. This suggests that
combining BRAF-targeted therapy with aldesleukin, which activates more of these white blood
cells, can lead to an increase in the death of cancer cells.
In this research study, we are looking to see whether the combination of vemurafenib, a
BRAF-inhibitor combined with aldesleukin, an immunotherapy drug, work together to produce a
better health outcome in people with metastatic melanoma.
(vemurafenib and aldesleukin) to learn whether the combination works in treating a specific
cancer. While both vemurafenib and aldesleukin are approved by the FDA for the treatment of
metastatic melanoma, the FDA has not yet approved the combination of vemurafenib and
aldesleukin.
Researchers have found that a large number of melanoma cells have mutations in the BRAF
gene. It has been shown that vemurafenib blocks the effects of these mutations in the BRAF
gene, and, as a result, may help to prevent cancer growth.
Aldesleukin, also referred to as IL-2, is an immunotherapy drug administered via IV infusion
that increases the growth of key cells within the immune system that are responsible for
targeting cancer cells. Activating more of these key cells, called T-lymphocytes and
natural-killer cells, leads to increased cancer cell death.
The BRAF gene is located on a larger pathway called the MAPK pathway. Studies have shown
that when a BRAF inhibitor, like vemurafenib is used to block the MAPK pathway, melanocytes,
or cancer cells express more proteins on their surfaces, making them easier for
T-lymphocytes and natural killer cells to recognize and kill them. This suggests that
combining BRAF-targeted therapy with aldesleukin, which activates more of these white blood
cells, can lead to an increase in the death of cancer cells.
In this research study, we are looking to see whether the combination of vemurafenib, a
BRAF-inhibitor combined with aldesleukin, an immunotherapy drug, work together to produce a
better health outcome in people with metastatic melanoma.
You will take oral vemurafenib twice a day for 2 weeks. Following this lead-in period, you
will receive aldesleukin via IV infusion on Day 15 of the study. One course of aldesleukin
is 12 weeks long; you will receive aldesleukin via IV infusion every 8 hours for the first
five days. Youi will be hospitalized for the 5 days that you are receiving aldesleukin. This
week that you are hospitalized will be referred to as Week 1. Week 1 of aldesleukin will be
days 15-19 (M-F) of the 12 week cycle. Following Week 1 of therapy, you will be discharged
from the hospital and only take vemurafenib at home for the following week. You wil then
come in for one more week of aldesleukin during days 29-33 of the 12 week cycle. This is
referred to as Week 2 of aldesleukin.
You will continue to take vemurafenib twice daily during the course of aldesleukin. Your
cancer will be evaluated at screening and at Week 12 following the beginning of the first
aldesleukin course with a CT scan. After the first cycle, your tumor will be evaluated every
8 weeks for the first year, then every 12 weeks for years 2 and 3, every 6 months for year
5, and annually thereafter.
During the research study, you will come into the clinic weekly for various tests and
procedures.
If scans show that your cancer has improved after the first course of aldesleukin, your
doctor may allow you to continue on the a second course. In the event of a second course of
aldesleukin, you will remain on vemurafenib throughout the second course. If your doctor
decides you will not receive a second course of aldesleukin, you may still remain on
vemurafenib until one of the following events occurs: Your cancer becomes worse, you
experience serious side effects that are from taking vemurafenib, you request to discontinue
taking vemurafenib/withdraw from the study, you develop another illness that prevents you
from being able to take vemurafenib, the study is terminated by the sponsor or your study
doctor decides it is in your best interest to discontinue treatment with vemurafenib.
In some cases if your cancer does get worse, but you and your study doctor believe you are
still benefitting from vemurafenib in some way, you may continue receiving it after you
consult with the study director.
After the final dose of the study drug we would like to keep track of your medical condition
for the rest of your life. We would like to do this by calling you on the telephone once a
year to see how you are doing. Keeping in touch with you and checking your condition every
year helps us look at the long-term effects of the research study.
will receive aldesleukin via IV infusion on Day 15 of the study. One course of aldesleukin
is 12 weeks long; you will receive aldesleukin via IV infusion every 8 hours for the first
five days. Youi will be hospitalized for the 5 days that you are receiving aldesleukin. This
week that you are hospitalized will be referred to as Week 1. Week 1 of aldesleukin will be
days 15-19 (M-F) of the 12 week cycle. Following Week 1 of therapy, you will be discharged
from the hospital and only take vemurafenib at home for the following week. You wil then
come in for one more week of aldesleukin during days 29-33 of the 12 week cycle. This is
referred to as Week 2 of aldesleukin.
You will continue to take vemurafenib twice daily during the course of aldesleukin. Your
cancer will be evaluated at screening and at Week 12 following the beginning of the first
aldesleukin course with a CT scan. After the first cycle, your tumor will be evaluated every
8 weeks for the first year, then every 12 weeks for years 2 and 3, every 6 months for year
5, and annually thereafter.
During the research study, you will come into the clinic weekly for various tests and
procedures.
If scans show that your cancer has improved after the first course of aldesleukin, your
doctor may allow you to continue on the a second course. In the event of a second course of
aldesleukin, you will remain on vemurafenib throughout the second course. If your doctor
decides you will not receive a second course of aldesleukin, you may still remain on
vemurafenib until one of the following events occurs: Your cancer becomes worse, you
experience serious side effects that are from taking vemurafenib, you request to discontinue
taking vemurafenib/withdraw from the study, you develop another illness that prevents you
from being able to take vemurafenib, the study is terminated by the sponsor or your study
doctor decides it is in your best interest to discontinue treatment with vemurafenib.
In some cases if your cancer does get worse, but you and your study doctor believe you are
still benefitting from vemurafenib in some way, you may continue receiving it after you
consult with the study director.
After the final dose of the study drug we would like to keep track of your medical condition
for the rest of your life. We would like to do this by calling you on the telephone once a
year to see how you are doing. Keeping in touch with you and checking your condition every
year helps us look at the long-term effects of the research study.
Inclusion Criteria:
- Histologically confirmed metastatic or unresectable melanoma with V600E mutation
- Measurable disease
- May have received prior immunotherapy (excluding interleukin 2)
- Life expectancy greater than 3 months
- Recovered from effects of previous surgery and/or traumatic injury
- Must agree to use effective contraception
Exclusion Criteria:
- Pregnant or breastfeeding
- Psychological, familial or other conditions that could hamper compliance with
protocol
- Receiving other study agents
- History of carcinomatous meningitis
- Known active brain metastases
- Have received a BRAF inhibitor
- Uncontrolled intercurrent illness
- HIV positive on antiretroviral therapy
- History of a different malignancy within past 5 years (except cervical cancer in situ
or basal/squamous cell carcinoma of the skin)
- Active hepatitis B or C
- Have received allogenic bone marrow transplant or organ transplant
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