Intervention: Vismodegib
Trial phase: Phase 1
ATC code: L01XJ01 | L01XX43
SMILES: CS(=O)(=O)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)c(Cl)c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 4
Group description: Participants received single dose of GDC-0449 hard gelatin capsules at 540 mg on Day 1, thereafter Day 8 received daily dose until disease progression, maximum benefit, or intolerability.
Eligibility criteria:
DISEASE CHARACTERISTICS:

Histologically confirmed locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists

Progressed after first-line and second-line therapy (if there is a second-line therapy that has been shown to provide clinical benefit)

Must receive standard second-line therapy if second-line therapy has been shown to provide clinical benefit

Evaluable disease by physical examination, imaging, and/or one of the following:

Two rising prostate-specific antigen (PSA) levels ≥ 2 weeks apart, with one obtained during screening (for patients with prostate cancer)
Two rising CA-125 levels ≥ 2 weeks apart, with one obtained during screening (for patients with ovarian cancer)
No CNS cancer, either primary lesions or metastatic disease, as the current malignancy
No pleural effusions, ascites, or leptomeningeal disease as the only manifestation of the current malignancy

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Granulocyte count ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Hemoglobin ≥ 9 g/dL
Serum bilirubin normal
Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN) (≤ 4 times ULN for patients with liver or bone metastases)
AST and ALT ≤ 1.5 times ULN (≤ 5 times the ULN for patients with liver metastases)
Serum creatinine ≤ 1.5 mg/dL
INR < 1.3
aPTT ≤ 1.5 times ULN
Fasting total serum cholesterol ≤ 220 mg/dL (without cholesterol-lowering drugs)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Able and willing to swallow pills
No malabsorption syndrome or other condition that would interfere with enteral absorption

No history of significant atherosclerotic disease, including the following:

Coronary artery disease (i.e., myocardial infarction within the past year or unstable angina)
Documented carotid atheromas
No history of congestive heart failure or ventricular arrhythmia requiring medication
No congenital long QT syndrome
No baseline QTc intervals > 0.47 seconds on two of three baseline 12-lead ECGs recorded during the screening period
No active infection requiring intravenous antibiotics
No known HIV infection
No uncontrolled hypocalcemia, hypomagnesemia, or hypokalemia, defined as less than the lower limit of normal for the institution despite adequate electrolyte supplementation
No history of clinically important liver disease, including cirrhosis or viral or other hepatitis
No current alcohol abuse
No significant traumatic injury within the past 3 weeks
No other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the study results or renders the patient at high risk from treatment complications

PRIOR CONCURRENT THERAPY:

At least 4 weeks since prior chemotherapy, investigational therapy, radiotherapy, or major surgical procedure and recovered
No concurrent medications with narrow therapeutic indices that are cytochrome P450 substrates (warfarin sodium [Coumadin®])

No concurrent medications known to prolong the QT interval, including any of the following:

Quinidine or other anti-arrhythmic agents
Haloperidol, fluoxetine, paroxetine, or sertraline
Pentamidine, fluoroquinolone, or macrolide antibiotics
No concurrent medications that may interfere with the metabolism of GDC-0449 (e.g., ketoconazole)
No concurrent grapefruit juice