Docetaxel, Cisplatin, and Fluorouracil in Treating Patients with Gastric or Gastroesophageal Junction Cancer That is Metastatic or Cannot Be Removed by Surgery

Inclusion Criteria

• Patients must have histologically or cytologically confirmed metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma; GEJ adenocarcinoma may be classified according to Siewert’s classification type I, II, or III
• Histological documentation of local recurrence or metastasis is strongly encouraged, unless the risk of such a procedure outweighs the potential benefit of confirming the metastatic disease; if no histologic confirmation, then the metastases or recurrence will require documentation by a 2nd radiographic procedure (eg. PET/computed tomography [CT] scan or magnetic resonance imaging [MRI] in addition to the CT scan); if the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation will be required
• Patients must have disease that can be evaluated radiographically; this may be measurable disease or non-measurable disease; measurable disease is defined as that which can be measured in at least one dimension as >= 20 mm with conventional techniques, or >= 10 mm by high resolution imaging; disease that is identified on radiology studies, but does not meet the criteria for measurable disease, is considered non-measurable
• Patients may have received no prior chemotherapy for metastatic or unresectable disease; patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration; patients may not have received prior docetaxel or cisplatin
• Karnofsky performance status >= 70% (Eastern Cooperative Oncology Group [ECOG] performance status 0-1)
• Peripheral neuropathy =< grade 1
• White blood cell count (WBC) >= 3000/mm^3
• Absolute neutrophil count (ANC) >= 1500 cells/mm^3
• Hemoglobin >= 9.0 g/dl
• Platelet count >= 100,000 /mm^3
• Total bilirubin =< 1.5
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and alkaline phosphatase must be within the eligible; in determining eligibility, the more abnormal of the two values (AST or ALT) should be used; patients with alkaline phosphatase elevation secondary to the bony metastases rather than liver dysfunction may proceed with treatment on protocol after discussion with the principal investigator
• Alkaline phosphatase =< upper limit of normal (ULN) and AST or ALT =< ULN eligible
• Alkaline phosphatase > 1 x ULN but =< 2.5 x ULN and AST or ALT =< ULN eligible
• Alkaline phosphatase > 2.5 x ULN but =< 5 x ULN and AST or ALT =< ULN eligible
• Alkaline phosphatase > 5 x ULN and AST or ALT =< ULN ineligible
• Alkaline phosphatase =< ULN and AST or ALT > 1 x ULN but =< 1.5 x ULN eligible
• Alkaline phosphatase > 1 x ULN but =< 2.5 x ULN and AST or ALT > 1 x ULN but =< 1.5 x ULN eligible
• Alkaline phosphatase > 2.5 x ULN but =< 5 x ULN and AST or ALT > 1 x ULN but =< 1.5 x ULN ineligible
• Alkaline phosphatase > 5 x ULN and AST or ALT > 1 x ULN but =< 1.5 x ULN ineligible
• Alkaline phosphatase =< ULN and AST or ALT > 1.5 x ULN but =< 5 x ULN eligible
• Alkaline phosphatase > 1 x ULN but =< 2.5 x ULN and AST or ALT > 1.5 x ULN but =< 5 x ULN ineligible
• Alkaline phosphatase > 2.5 x ULN but =< 5 x ULN and AST or ALT > 1.5 x ULN but =< 5 x ULN ineligible
• Alkaline phosphatase > 5 x ULN and AST or ALT > 1.5 x ULN but =< 5 x ULN ineligible
• Alkaline phosphatase =< ULN and AST or ALT > 5 x ULN ineligible
• Alkaline phosphatase > 1 x ULN but =< 2.5 x ULN and AST or ALT > 5 x ULN ineligible
• Alkaline phosphatase > 2.5 x ULN but =< 5 x ULN and AST or ALT > 5 x ULN ineligible
• Alkaline phosphatase > 5 x ULN and AST or ALT > 5 x ULN ineligible
• Serum creatinine =< 1.5 mg/dl; if serum creatinine is 1.2-1.5 mg/dl, the creatinine clearance (either measured or calculated) must be 50 ml/min or greater
• The patient has a prothrombin time (PT) (international normalized ratio [INR]) =< 1.5 and a partial thromboplastin time (PTT) =< 3 seconds above the upper limits of normal if the patient is not on anticoagulation; if a patient is on full-dose anticoagulants, the following criteria should be met for enrollment: * The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of low molecular weight (LMW) heparin * The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices)
• Women of childbearing potential have a negative pregnancy test
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
• Ability to understand informed consent and signing of written informed consent document prior to initiation of protocol therapy
• Patients must have HER2-positive (fluorescence in situ hybridization [FISH]+ or immunohistochemistry [ICH] 3+) metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma to be eligible for trastuzumab; for the purposes of this protocol, FISH+ is defined as HER2:centromeric probe for chromosome 17 (CEP17) ratio >= 2.0; biopsy samples with cohesive IHC3+ or FISH+ clones are considered HER2 positive irrespective of size, i.e. < 10%; FISH+ defined as > 2 HER2:CEP17; Note: samples will be processed locally in the laboratory of investigational sites; the results of local laboratory HER2 analysis will be required and sufficient to start the study treatment; the Memorial Sloan-Kettering (MSK) laboratory will be used for subsequent confirmation of HER2 status; MSK pathology review will not be required to begin therapy on the protocol; samples provided to the MSK laboratory must either be HER2 IHC slides, or if FISH confirmation is necessary, a paraffin block(s) of adequate size to allow if possible for at least 5 slides with cuts that are 5-microns thick or if a paraffin block is not available, then if possible at least 5 slides with cuts that are 5-microns thick will be acceptable; archived or fresh tumor samples may be used
• Patients who are receiving trastuzumab must have a left ventricular ejection fraction of >= 50%

Exclusion Criteria

• Patients who have received previous chemotherapy for the treatment of metastatic or unresectable gastric or GEJ adenocarcinoma are ineligible; patients who have received previous pre- or post-operative chemotherapy or chemoradiation are ineligible if therapy was completed less than 6 months prior to study registration; patients must have recovered from adverse events from any previous therapy
• Patients who have received previous docetaxel or cisplatin
• Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer
• Patients with brain or central nervous system metastases, including leptomeningeal disease
• Pregnant (positive pregnancy test) or breast feeding
• Serious, non-healing wound, ulcer, or bone fracture
• Significant cardiac disease as defined as: unstable angina, New York Heart Association (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction within 6 months
• Evidence of bleeding diathesis or coagulopathy
• History of a stroke or cerebrovascular accident (CVA) within 6 months
• Clinically significant peripheral vascular disease
• Clinically significant hearing loss or ringing in the ears
• Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80
• Inability to comply with study and/or follow-up procedures
• Patients with any other medical condition or reason, in that investigator’s opinion, makes the patient unstable to participate in a clinical trial
• For patients who are Her2 positive and will be treated on the trastuzumab + mDCF cohort, prior trastuzumab treatment is not allowed
• For patients who are Her2 positive and will be treated on the trastuzumab + mDCF cohort, left ventricular function < 50%