Sorafenib, Docetaxel, and Cisplatin in Treating Patients With Metastatic or Advanced Gastric or Gastroesophageal Junction Cancer

PRIMARY OBJECTIVES:

I. To evaluate the response rate (complete response and partial response) of the combination of BAY 43-9006 with docetaxel and cisplatin or oxaliplatin in patients with gastric and GEJ adenocarcinoma.

II. To evaluate the progression-free survival (PFS) and overall survival.

III. To evaluate the toxicities of BAY 43-9006 in patients with advanced and metastatic gastric or GEJ adenocarcinoma combined with docetaxel/cisplatin or docetaxel/oxaliplatin.

IV. To evaluate Raf status in the tumor and to correlate response and PFS to the presence or absence of an activating mutation in B-Raf.

V. To analyze the pharmacokinetic and pharmacogenetic properties of BAY 43-9006 including angiogenesis, monooxygenases, polymorphisms and multidrug-resistance (MDR). This study will be conducted via the E1Y03 mechanism.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to Siewert's tumor location (I vs II vs III) and extent of disease (locally advanced unresectable vs distant metastases).

Patients receive oral BAY 43-9006 twice daily on days 1-21. Patients also receive docetaxel intravenously (IV) over 1 hour and cisplatin IV over 1-2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 3 years.

An addition of an arm containing oxaliplatin was proposed after meeting the accrual goal but did not move forward and the study was closed to accrual in July, 2007 with a final accrual of 44 patients.

Inclusion criteria

• Patients must have measurable, histologically confirmed, advanced unresectable or metastatic gastric or GEJ adenocarcinoma; imaging studies must be conducted within 4 weeks of study entry
• For patients with GEJ adenocarcinoma, the tumor location should be specified using the Siewert classification used in other NCI-sponsored Phase II studies in these disease sites
• Patients must have an ECOG performance status of 0-1
• Patients may have had adjuvant chemotherapy or chemoradiation therapy, with or without 5-Fluorouracil if the treatment was performed more than 6 months before any evidence of recurrent or metastatic disease
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Must have the following baseline laboratory values obtained within 2 weeks of registration:

• Absolute Granulocyte Count >= 1,500/mm^3
• Platelet Count >= 100,000/mm^3
• White Blood Count >= 3,000/mm^3
• Serum Creatinine <= 1.5 mg/dl
• Total Bilirubin <= 2.0 mg/dl
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (Alk phos) <= 2.5 x upper limit of normal
• Patients must be able to take oral medication without crushing, dissolving or chewing tablets

Exclusion criteria

• Prior radiotherapy, chemotherapy or investigational therapies, particularly inhibitors of tyrosine Kinases, signal transduction or angiogenesis in the treatment for their recurrent and/or metastatic gastric or GEJ adenocarcinoma
• Receiving any other investigational agents
• Being pregnant or breast-feeding; all females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy
• HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006
• Brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006
• Acute active infection with significant clinical intervention per physician's discretion
• Previous or concurrent malignancies are not allowed, except:

• Non-melanoma skin cancer and in situ cervical cancer
• Treated cancer from which the patient has been continuously disease-free for more than five years
• Other uncontrolled intercurrent illnesses including, but not limited to: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/addictive disorders that would limit compliance with study requirements
• Evidence of bleeding diathesis
• Concurrent cytochrome P450 enzyme-inducing anti-epileptic drugs:

• Phenytoin
• Carbamazepine
• Phenobarbital
• Rifampin
• St. John's Wort