Vemurafenib:Radiation Use During Vemurafenib Treatment
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Skin Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/8/2015 |
| Start Date: | August 2014 |
| End Date: | December 2016 |
There is a lack of safety data regarding the combination of radiation and vemurafenib. The
lack of data is due to the early and late stage clinical studies with vemurafenib excluding
concomitant or closely scheduled radiation therapy. There have been anecdotal observations
of increased radiotoxicity when giving full doses of radiation therapy concomitantly with
vemurafenib. The rate of these reactions is presently not known nor is the mechanism,
though the toxicity may be due to radiation enhancement. Therefore, there is a pressing
need for information and guidance for a clinical scenario that will become very common now
that vemurafenib is approved by the FDA and widely used in the community. Furthermore,
future studies in melanoma using radiation combined with BRAF inhibition will be possible
only after good safety data are established.
Although highly successful in creating tumor responses in BRAFV600 mutant metastatic
melanoma, the progression free survival remains, on average, 6 months with vemurafenib. A
very common emerging problem exists when patients have had a dramatic tumor response to
vemurafenib at multiple sites, but later progress in a few areas which may be symptomatic;
this scenario can be defined as oligoprogressive disease. Of those vemurafenib treated
patients who have progressive disease, the percentage of patients who progress in this way
is approximately 45%. A common and widely used approach to treat oligoprogressions for
melanoma patients on other chemotherapy or immunotherapy is to treat the progressive or
symptomatic areas with radiation or surgery, while continuing on a systemic treatment which
has overall clinical benefit to the patient. Small numbers of patients with
oligoprogressions on vemurafenib have been treated with radiation and/or surgery and have
enjoyed significant progression free survival. In fact those eligible for this approach had
a median overall survival of >9.1 months vs. 3.4 months for those who did not undergo local
therapy and resume vemurafenib due to multiple progressing areas. Furthermore, the patients
in the oligoprogressive population (73% Stage IV M1c), had a median OS of >25.5 months which
is more than would be expected for patients with disease this advanced. The longer term
follow up of these patients will be reported soon. These preliminary data suggest that
treating oligoprogressions with local therapy followed by continued vemurafenib will be
advantageous.
lack of data is due to the early and late stage clinical studies with vemurafenib excluding
concomitant or closely scheduled radiation therapy. There have been anecdotal observations
of increased radiotoxicity when giving full doses of radiation therapy concomitantly with
vemurafenib. The rate of these reactions is presently not known nor is the mechanism,
though the toxicity may be due to radiation enhancement. Therefore, there is a pressing
need for information and guidance for a clinical scenario that will become very common now
that vemurafenib is approved by the FDA and widely used in the community. Furthermore,
future studies in melanoma using radiation combined with BRAF inhibition will be possible
only after good safety data are established.
Although highly successful in creating tumor responses in BRAFV600 mutant metastatic
melanoma, the progression free survival remains, on average, 6 months with vemurafenib. A
very common emerging problem exists when patients have had a dramatic tumor response to
vemurafenib at multiple sites, but later progress in a few areas which may be symptomatic;
this scenario can be defined as oligoprogressive disease. Of those vemurafenib treated
patients who have progressive disease, the percentage of patients who progress in this way
is approximately 45%. A common and widely used approach to treat oligoprogressions for
melanoma patients on other chemotherapy or immunotherapy is to treat the progressive or
symptomatic areas with radiation or surgery, while continuing on a systemic treatment which
has overall clinical benefit to the patient. Small numbers of patients with
oligoprogressions on vemurafenib have been treated with radiation and/or surgery and have
enjoyed significant progression free survival. In fact those eligible for this approach had
a median overall survival of >9.1 months vs. 3.4 months for those who did not undergo local
therapy and resume vemurafenib due to multiple progressing areas. Furthermore, the patients
in the oligoprogressive population (73% Stage IV M1c), had a median OS of >25.5 months which
is more than would be expected for patients with disease this advanced. The longer term
follow up of these patients will be reported soon. These preliminary data suggest that
treating oligoprogressions with local therapy followed by continued vemurafenib will be
advantageous.
Inclusion Criteria:
- Age > 18 years old
- Diagnosis of BRAFV600 mutated Stage IV or unresectable Stage III melanoma
- Actively receiving treatment with vemurafenib as single agent and tolerating at least
720 mg bid for one cycle (28 days).
- In the opinion of the investigator, patients who are progressing in an area where
radiation may provide benefit from either:
- Symptom control
- Oligo-progression, defined as progression in up to 3 areas where focal treatment
would provide benefit.
- Patients with brain metastases will be allowed provided they meet all of the
following criteria:
- Small, < 1cm metastases which are untreated are allowed so long as in the
opinion of the investigator they do not require immediate treatment by radiation
or surgery
- Asymptomatic, treated brain metastases which are stable for 4 weeks prior to
study entry are allowed
- If patients are requiring steroids for their brain metastases, they must be on a
stable dose for two weeks prior to study entry, and maintain that steroid dosing
during the radiation treatments
- Adequate bone marrow function as defined by: ANC > 1.0 k/uL, Platlets > 100 k/uL,
Hemoglobin > 9 g/dL
- Adequate hepatic function: Total bilirubin < 1.5 times the institutional upper limit
of normal, ALT/AST < 2.5 times the institutional upper limit of normal
- Adequate renal function as defined by serum creatinine < 1.5 times the upper limit of
normal.
- Negative serum pregnancy test at screening for women of child bearing potential
within 10 days of starting vemurafenib treatment. Women of non-childbearing
potential may be included if they are either surgically sterile or have been
postmenopausal for > 1 year
- Fertile men and women must agree to use an acceptable method of birth control during
treatment and for at least 2 months after discontinuation of vemurafenib.
- Able and willing to provide informed consent to an approved consent form that
conforms to federal and institutional guidelines.
Exclusion Criteria:
- Screening QTc interval > 450 msec on EKG
- Known HIV positivity or AIDS-related illness, or active HBV, or active HCV.
- Any of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, serious cardiac arrhythmia requiring
medication, uncontrolled hypertension, cerebrovascular accident or transient ischemic
attack, or symptomatic pulmonary embolism.
- Malabsorption disorder that would preclude adequate vemurafenib absorption.
- Other medical condition present that in the opinion of the investigator will hinder
the subjects ability to complete the study.
We found this trial at
1
site
2000 Circle of Hope Dr
Salt Lake City, Utah 84112
Salt Lake City, Utah 84112
(801) 585-0303
Huntsman Cancer Institute at University of Utah Huntsman Cancer Institute (HCI) is part of the...
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