Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma
Condition: Gastroesophageal Junction Adenocarcinoma; Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms
Intervention: Docetaxel, Leucovorin, Fluorouracil, Cisplatin; Docetaxel, Cisplatin, Fluorouracil, Neulasta, or Neupogen; Docetaxel, Leukvorin, Flurouracil, Cisplatin, Trastuzumab
Intervention description: Drug Dose (mg/m2) Schedule Docetaxel 40 Day 1 IVPB (60 min) Leucovorin 400 Day 1 IVPB (30 min) Fluorouracil 400 IVP day 1 Fluorouracil 1000 IVCI x 48 hours Cisplatin 40 Day 2 OR 3 IVPB (30 min); Drug Dose (mg/m2) Schedule Docetaxel 75 Day 1 IVPB (60 min) Cisplatin 75 Day 1 IVPB (60 min) Fluorouracil 750 IVCI daily x 5 days Neulasta 6 mg subcut on d 8, 9, or 10 or Neupogen 300 or 480 mcg* subcut x 7 d 10-17
* 300 mcg for weight < 60 kg, 480 mcg for weight > 60 kg
Arm B is repeated every 3 weeks, and a cycle will be considered every 6 weeks (eg 2 treatments). Tumor assessments will be performed following the completion of every cycle for the first 6 cycles, and then every 2 cycles thereafter.; Treatment for Her2 Positive Participants
Docetaxel 40 Day 1 IVPB (60 min) Leucovorin 400 Day 1 IVPB (30 min) Fluorouracil 400 IVP day 1 Fluorouracil 1000 mg/m2/d daily x 2 days Cisplatin 40 Day 2 OR 3 IVPB (30 min) Trastuzumab Administered on an every 2 week dosing schedule. Initial loading dose of 6 mg/kg over 90 minutes, followed by trastuzumab 4 mg/kg every 2 weeks over 30 minutes.
Intervention MeSH terms: Leucovorin; Cisplatin; Docetaxel; Fluorouracil; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 111.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: gastroesophageal junction; gastric cancer; adenocarcinoma; unresectable gastric cancer; metastatic gastric

Summary:

      Chemotherapy given together is a standard way to treat your cancer. One standard treatment
      includes a combination of docetaxel, cisplatin, and fluorouracil. However, the original
      combination of these three drugs can cause many side effects. This study is being done to
      find out if these three drugs can be given at lower doses more often, with fewer side effects
      and still maintain the same benefit as the standard way of giving this three drug
      combination. If your tumor overexpresses a protein called Her2, you are also eligible to
      receive trastuzumab with chemotherapy. Trastuzumab is a medicine that has been approved by
      the US Food and Drug Administration for the treatment of Her2 positive breast cancer.
      Trastuzumab is now also a standard treatment in combination with chemotherapy for the
      treatment of Her2 positive stomach cancer. If your tumor is Her2 positive, you would receive
      the modified administration schedule of docetaxel, cisplatin, and fluorouracil with
      trastuzumab.
    

Eligibility criteria:

        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[43].

          -  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/CT scan or 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.

          -  Age 18 years or older.

          -  Karnofsky performance status > than or = to 70% (ECOG performance status 0-1).

          -  Peripheral neuropathy < than or = to grade 1.

          -  Hematologic (minimal values):

               -  White blood cell count > than or = to 3000/mm3

               -  Absolute neutrophil count > than or = to 1500 cells/ mm3

               -  Hemoglobin > than or = to 9.0 g/dl

               -  Platelet count > than or = to 100,000 / mm3

          -  Hepatic (minimal values):

          -  Total bilirubin < or = to 1.5

             * * AST and ALT and Alkaline phosphatase must be within the eligible range. 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.

          -  Kidney function (minimal values):

             * Serum creatinine < than or = to 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 PT (INR) < than or = to 1.5 and an PTT < than or = to 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 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 (FISH+ or IHC 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: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.

          -  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 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%