| Inclusion Criteria: | 1) Signed informed consent.
2) Men and women age >/= 18 years
3) ECOG performance status 0, 1, or 2
4) For patients with mBCC, histologic confirmation of distant BCC metastasis (e.g., lung, liver, lymph nodes, or bone), with metastatic disease that is RECIST measurable using CT or MRI. If a patient with locally advanced BCC also has a tumor that is not contiguous with cutaneous BCC, e.g., regional lymph nodes (if confirmed on biopsy as BCC and RECIST measurable), the patient should be considered as having mBCC and should be enrolled in the mBCC cohort.
5) For patients with locally advanced BCC, histologically confirmed disease that is considered to be inoperable or medical contraindication to surgery, in the opinion of a Mohs dermatologic surgeon, head and neck surgeon, or plastic surgeon
6) Acceptable medical contraindications to surgery include: a.) BCC that has recurred in the same location after two or more surgical procedures and curative resection is deemed unlikely; b.) anticipated substantial morbidity and/or deformity from surgery (e.g., removal of all or part of a facial structure, such as nose, ear, eyelid, eye; or requirement for limb amputation); c.) other conditions considered to be medically contraindicating must be discussed with the Medical Monitor before enrolling the patient.
7) For patients with locally advanced BCC, radiotherapy must have been previously administered for their locally advanced BCC, unless radiotherapy is contraindicated or inappropriate (e.g., hypersensitivity to radiation due to genetic syndrome such as Gorlin syndrome, limitations because of location of tumor, or cumulative prior radiotherapy dose). For patients whose locally advanced BCC has been irradiated, disease must have progressed after radiation.
8) Patients with nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above.
9) For patients with locally advanced BCC, willingness to consent to biopsy of tumor(s) at baseline and during the study, as mandated by the protocol
10) For all patients, representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report, obtained at any time prior to entry of study
11) Adequate hematopoietic capacity, as defined by the following: Hemoglobin > 8.5 g/dL and not transfusion dependent Granulocyte count >/= 1000/microL Platelet count >/= 75,000/microL
12) Adequate hepatic function, as defined by the following: AST (aspartate aminotransferase) and ALT(alanine transaminase) </= 3 × the upper limit of normal (ULN) Total bilirubin </= 1.5 × the ULN or within 3 × the ULN for patients with Gilbert disease
13) Adequate renal function, as defined by the following: Serum creatinine </= 2.0 mg/dL or calculated creatinine clearance > 50 mL/min
14) For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 7 months after discontinuation of GDC-0449.
15) For men with female partners of childbearing potential, agreement to use a condom, and to advise their female partner to use an additional method of contraception during the study and for 7 months after discontinuation of GDC-0449
16) Agreement not to donate blood or blood products during the study and for 7 months after discontinuation of GDC-0449; for male patients, agreement not to donate sperm during the study and for 7 months after discontinuation of GDC-0449 |