A Phase II Study of Radiation Therapy and Vismodegib, for the Treatment of Locally Advanced Basal Cell Carcinoma of the Head and Neck
1. 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
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.
2. 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.
3. Zubrod Performance Status 0-2
4. Age of greater than or equal to 18 years
5. Adequate bone marrow and organ function defined as follows:
Adequate bone marrow function:
leukocytes: > 3,000/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 ULN or within 3x the ULN
for patients with Gilbert disease AST(SGOT): < 3 X institutional upper limit of
normal ALT(SGPT): < 3 X institutional upper limit of normal
Adequate renal function:
creatinine: within normal institutional limits OR creatinine clearance: > 60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal
6. 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.
1. Patients with distant metastasis (e.g. spread to distant areas outside the regional
lymph nodes, clearly non contiguous areas of bone involvement, or distant metastasis
to lung, brain, liver or other visceral organs) are ineligible.
2. Patients with nevoid BCC syndrome (Gorlin syndrome) should not enroll in this study.
3. Known other malignancy within 3 years (except for tumors with a negligible risk for
metastasis or death, such as adequately treated basal cell or squamous cell carcinoma
of the skin, ductal carcinoma in situ of the breast, carcinoma in situ of the cervix,
differentiated thyroid carcinoma considered in remission, or the presence of prostate
cancer confined to the prostate with a PSA < 1 for more than 6 months; the presence
of other stage I basal cell carcinomas is allowed);
4. Prior vismodegib or other antagonists of the Hh pathway;
5. Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other
targeted therapy, topical therapy such as 5-Fluorouracil or imiquimod, radiation
therapy, surgery, or photodynamic therapy.
- For patients with multiple cutaneous BCCs at baseline that are not designated by
the investigator as target lesions, treatment of these non-target BCCs with
surgery may be permitted but must be discussed with Data Coordinator prior to
any surgical procedure.
6. Recent (within 4 weeks of Registration), current, or planned participation in another
experimental drug study.
7. Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields in such a way that curative intent with radiation cannot be
8. Inability or unwillingness to swallow capsules; Patients with any condition that may
impair the ability to swallow or absorb oral medications/investigational product
- any lesion, whether induced by tumor, radiation or other conditions, which makes
it difficult to swallow capsules or pills;
- prior surgical procedures affecting absorption including, but not limited to
major resection of stomach or small bowel;
- active peptic ulcer disease;
- malabsorption syndrome
9. Pregnant or lactating women. Patients who are unable or are unwilling to adhere to
the required contraceptive methods are excluded from the study.
- Women of reproductive potential are required to use two forms of acceptable
contraception (including one acceptable barrier method with spermicide) during
therapy and for 7 months after completing therapy. Acceptable forms of primary
contraception include the following: Combination hormonal contraceptives,
subcutaneous hormonal implant, hormonal patch, hormonal contraceptives
(levonorgestre-releasing intrauterine system, medroxyprogesterone acetate
depot), tubal sterilisation, vasectomy and intrauterine device (IUD).
Acceptable forms of barrier contraception include the following: Any male condom
(with spermicide) or diaphragm (with spermicide).
- Male patients must use condoms at all times, even after a vasectomy, during
sexual intercourse with female partners of reproductive potential during
treatment with vismodegib and for 2 months after the last dose to avoid exposing
a pregnant partner and unborn fetus to vismodegib.
10. Life expectancy of <12 weeks
11. Patients with widespread superficial multifocal BCC who are considered unresectable
due to breadth of involvement and do not have a single definable area of disease
amenable to radiation therapy targeting.
Note: If an area including one or more lesions is definable for radiation therapy
targeting, the patient may be eligible for treatment on study using the designated
target lesion(s) identified by the investigator.
12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
13. History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates use of an investigational drug or that might affect
interpretation of the results of the study or renders the patient at high risk form
14. HIV-positive patients on combination antiretroviral therapy, because of the potential
for pharmacokinetic interactions with vismodegib;