A Study of Hedgehog Pathway Inhibitor GDC-0449 in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists
Condition: Solid Cancers
Intervention: GDC-0449; GDC-0449; GDC-0449
Intervention description: Daily oral repeating dose; Three times weekly oral repeating dose; Once weekly oral repeating dose
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hedgehog; BCC; basal cell carcinoma

Summary:

      This is a two stage, Phase Ib study designed to describe the pharmacokinetics of GDC-0449 in
      patients with advanced solid tumors that are refractory to treatment or for whom no standard
      therapy exists.
    

Eligibility criteria:

        Inclusion Criteria

          -  Histologically documented, incurable, locally advanced or metastatic solid malignancy
             that has progressed after first-line and second-line therapy (if there is a
             second-line therapy that has been shown to provide clinical benefit); patients with
             basal cell carcinoma will be excluded from this study unless they do not qualify for
             another open GDC-0449 clinical trial

          -  For patients with disease that is evaluable by physical examination only, diagnosis
             must also include biomarker confirmation

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Documented negative pregnancy test for women of childbearing potential and agreement
             to use an effective form of contraception for the duration of the study

          -  Adequate hematopoietic capacity

          -  Adequate hepatic function

          -  Adequate renal function

          -  At least 3 weeks since last chemotherapy, investigational agent, radiation therapy, or
             major surgical procedure and recovery to pre-treatment baseline or stabilization of
             all treatment-related toxicities

        Exclusion Criteria

          -  Known, untreated central nervous system (CNS) malignancies or treated brain metastases
             that are not radiographically stable for ≥ 3 months

          -  Active infection requiring intravenous (IV) antibiotics

          -  Clinically significant history of liver disease, including cirrhosis, current alcohol
             abuse, or current known active infection with hepatitis

          -  Any medical condition or diagnosis that would likely impair absorption of an orally
             administered drug (e.g., gastrectomy, ileal bypass, chronic diarrhea, gastroparesis)

          -  Any other diseases, 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 results or renders the patient at high risk from treatment
             complications

          -  Pregnant or lactating

          -  Treatment with excluded medications, including strong CYP450 inhibitors and inducers