Phase II Study of Radiation Therapy and Vismodegib for Advanced Head/Neck Basal Cell Carcinoma

Inclusion Criteria

• Patients with locally advanced BCC of the head and neck, consisting of at least one histologically or cytologically confirmed lesion greater than or equal to 20 mm in longest diameter that is considered to be inoperable or to have a medical contraindication to surgery, in the opinion of a Mohs dermatologic surgeon, head and neck surgeon, or plastic surgeon. Locally advanced disease is considered to include involved lymph nodes of the neck. A patient with regionally involved lymph nodes in the neck is considered eligible. The patient should be considered a candidate for radiotherapy and should not have medical contraindications to receipt of radiation therapy.

If a patient has distant metastatic spread of BCC (e.g., spread to distant areas outside the regional lymph nodes, clearly non contiguous areas of bone involvement, or distant metastasis to lung, brain, or other visceral organs), the patient should be considered as having distant metastasis and is not eligible.

Note: All lesions that the investigator proposes to follow as target lesions during the course of the study must have previously been histologically confirmed as BCC.

Acceptable contraindications to surgery include:

• BCC that has recurred in the same location after two or more surgical procedures and successful curative resection is deemed unlikely
• Complete surgical resection is not possible or is deemed excessively morbid (e.g. invasion into cranial nerves or skull base, proximity to brain, spinal canal, or orbit)
• Anticipated substantial morbidity and/or major deformity from surgery (e.g. removal of a major facial structure, such as nose, ear, eyelid, eye, or jaw; or requirement for upper limb amputation)
• Medical contraindication to surgery
• Patient refusal of surgery due to anticipated morbidity
• Other conditions considered to be contraindicating must be discussed with Data Coordinator before enrolling the patient.
• Prior radiation therapy is acceptable but there cannot be major overlap of the previously irradiated tissues with the new radiation treatment volumes anticipated to be delivered for the purposes of this protocol, in such a way that curative intent with radiation cannot be met. Furthermore, the total dose from all radiation delivered and expected to be delivered should not exceed the suggested dose constraints given for normal structures.
• Zubrod Performance Status 0-2
• Age of greater than or equal to 18 years
• Adequate bone marrow and organ function defined as follows:

Adequate bone marrow function:

leukocytes:> 3,000/microliter (mcL) absolute neutrophil count: greater than or equal to 1000 cells/mm3 platelets: greater than or equal to 75,000 cells/mm3 hemoglobin: greater than or equal to 8.5 g/dl (recommended cutoff subject to judgment of medical oncologist), but cannot be transfusion dependent

Adequate hepatic function:

total bilirubin: less than or equal to 1.5x institutional upper limit of normal (ULN) or within 3x the ULN for patients with Gilbert disease aspartate aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) : 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• Agreement not to donate blood or blood products during the study and for 7 months after discontinuation of vismodegib; for male patients, agreement not to donate sperm during the study and for 7 months after discontinuation of vismodegib.
• For male patients, agreement not to donate sperm during the study and for 3 months after the final dose of vismodegib. Male patients must use condoms at all times, even after a vasectomy, during sexual intercourse with pregnant partners or female partners of reproductive potential during treatment with vismodegib. Vismodegib is present in semen. It is not known if the amount of vismodegib in semen can cause embryo-fetal harm.
• Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating vismodegib. For wome