Efficacy and Safety of Sunitinib in Metastatic Gastric Cancer

Inclusion Criteria

• Signed and dated informed consent of the patient before the start of specific protocol procedures
• Histologically proven adenocarcinoma of stomach, esophagogastric junction or lower esophagus (Barrett carcinoma)
• Measurable metastatic disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). If locally recurrent disease, it must be associated with at least one measurable lymph node (> 20 mm by computed tomography [CT] scan or > 10 mm with spiral CT).
• Failure of prior palliative chemotherapy/chemotherapies (at least one irinotecan- or cisplatin-based). Failure is defined either by progression of disease or by significant toxicity that precludes further treatment.
• At least 3 weeks from previous chemotherapy at first dose of trial drug
• Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 National Cancer Institute-Common Toxicity Criteria (NCI-CTC) (except for the laboratory values)
• Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin ≤ 1.5 x ULN
• Absolute neutrophil count (ANC) ≥1500/microL
• Platelets ≥ 100,000/microL
• Hemoglobin ≥ 8.0 g/dL without support of growth factors (previous administration of erythrocyte concentrate is allowed)
• Serum calcium ≤ 12.0 mg/dL
• Serum creatinine ≤ 2.0 x ULN
• Lipase/amylase ≤ 2.5 x ULN
• All other laboratory values specified in the protocol (white blood cell count, white blood cell differential, alkaline phosphatase, sodium, potassium, creatinine clearance): resolution of all side effects of prior therapy or surgical procedure to grade 12 weeks
• Patients must be able to swallow sunitinib capsules
• Patients who understand the nature of the trial and are willing and able to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures
• Female patients who are capable of bearing children must have a negative pregnancy test result (serum or urine) at trial entry. All women included in the trial must be surgically sterile or postmenopausal or agree to employ adequate birth control measures for the duration of the trial and six months post-dosing. Male patients must be surgically sterile or must agree to use effective contraception during the trial and six months post-dosing.

Exclusion Criteria

• Tumor type other than adenocarcinoma (e.g., leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix which has been effectively treated. Patients curatively treated and disease free for at least 5 years will be discussed with the sponsor before inclusion.
• Patients with known brain or leptomeningeal metastasis
• Intake of non-permitted concomitant drugs. (The coordinating investigator should be contacted to discuss the individual case.)
• Concomitant treatment with antiarrhythmics and drugs with dysrhythmic potential (i.e., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, and indapamide)
• Administration of potent CYP34A inhibitors during or within 7 days before start of sunitinib-treatment (e.g. ketoconazole, itraconazole, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, indinavir, saquinavir, ritonavir, atazanavir, nelfinavir, grapefruit juice)
• Administration of potent CYP3A4 inducers during or within 12 days before start of sunitinib-treatment (e.g. dexamethasone, rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John´s wort, efavirenz, tipranavir)
• Ongoing treatment with therapeutic doses of anticoagulants such as Coumadin or heparins. (However, low dose Coumadi