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

• Serious toxicities, monitored through the adverse event reporting system and the standard ECOG toxicity analysis [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
• Overall survival [ Time Frame: From the date of entry on study, assessed up to 3 years ] [ Designated as safety issue: No ]
  Estimated using the method of Kaplan-Meier.
• Progression-free survival [ Time Frame: From the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression or death, assessed up to 3 years ] [ Designated as safety issue: No ]
  Estimated using the method of Kaplan-Meier.

This phase II trial is studying how well giving sorafenib together with docetaxel and cisplatin works in treating patients with metastatic or locally advanced gastric or gastroesophageal junction cancer that cannot be removed by surgery. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with docetaxel and cisplatin may kill more tumor cells

PRIMARY OBJECTIVES:

I. To evaluate the response rate (CR and PR) 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 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 sorafenib twice daily on days 1-21. Patients also receive docetaxel 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.

• Adenocarcinoma of the Gastroesophageal Junction
• Recurrent Gastric Cancer
• Stage IIIA Gastric Cancer
• Stage IIIB Gastric Cancer
• Stage IIIC Gastric Cancer
• Stage IV Gastric Cancer

• Drug: sorafenib tosylate
  Given orally
  Other Names:

  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
• Drug: docetaxel
  Given IV
  Other Names:

  • RP 56976
  • Taxotere
  • TXT
• Drug: cisplatin
  Given IV
  Other Names:

  • CACP
  • CDDP
  • CPDD
  • DDP

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
• Patients must NOT have had any previous 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
• Patients may not be receiving any other investigational agents
• The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, 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; women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood or urine test within 2 weeks prior to randomization to rule out pregnancy
• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006
• Patients must not have known brain metastases because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006
• 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
• AST/ALT/Alk phos =< 2.5 x ULN
• Patients must not have an 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
• Patients must not have 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
• Patients must not have any evidence of bleeding diathesis
• Patients must be able to take oral medication without crushing, dissolving or chewing tablets

• Patients must not be taking the following cytochrome P450 enzyme-inducing anti-epileptic drugs:

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