Radiation Use During Vemurafenib Treatment

Patients will be treated with vemurafenib plus radiation therapy (RT) based upon the
administration schedule. The starting dose of vemurafenib will be the patient's baseline
tolerating dose, between 720 - and 960 mg by mouth. Patients must be tolerating at a minimum
720mg for one cycle (28 days) prior to enrollment.

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, Platelets > 75 k/uL,
Hemoglobin > 8 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 creatinin < 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.