GDC-0449 in Treating Patients With Locally Advanced or Metastatic Solid Tumors

• Status: Completed
• Trial end date: 2009-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Collaborators: National Cancer Institute (NCI); Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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