GDC-0449 in Treating Patients With Locally Advanced or Metastatic Solid Tumors
Condition: Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Neoplasms
Intervention: GDC-0449
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: unspecified adult solid tumor, protocol specific

Summary:

      RATIONALE: Drugs used in chemotherapy, such as GDC-0449, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing.

      PURPOSE: This phase I trial is studying the side effects and best dose of GDC-0449 in
      treating patients with locally advanced or metastatic solid tumors.
    

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