Study of Docetaxel, Cisplatin, and Fluorouracil (Modified DCF) With Bevacizumab in Patients With Unresectable or Metastatic Gastroesophageal Adenocarcinoma
Condition: Stomach Neoplasms; Esophageal Neoplasms
MeSH terms: Neoplasms; Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms
Intervention: Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Intervention description: Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
Intervention MeSH terms: Leucovorin; Bevacizumab; Docetaxel; Fluorouracil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; Gastroesophageal; Docetaxel; Cisplatin; Fluorouracil; Bevacizumab; Metastatic Gastroesophageal Adenocarcinoma; 06-096

Summary:

      This study is being done to find out what effects a drug named/called bevacizumab has on
      patients and patients' tumors when given together with standard chemotherapy drugs. Making
      new blood vessels seems to be important for many tumors to grow. Bevacizumab is a new type of
      treatment for cancer that blocks the growth of new tumor blood vessels. In this study, the
      researchers will combine bevacizumab with chemotherapy drugs that are standard for the
      patient's disease and include cisplatin, docetaxel, fluorouracil, and leucovorin. The way the
      original combination of cisplatin, docetaxel, and fluorouracil was given caused many side
      effects including gastrointestinal symptoms, weakness, and a drop in the blood count of
      infection fighting cells. For this study, the researchers have modified this combination to
      give lower doses of the medicines more often, to reduce side effects from the chemotherapy.
      Patients will receive bevacizumab with this modified combination of docetaxel, cisplatin, and
      fluorouracil. This study is called a phase II study. In this study, everyone will have
      similar tumors and receive the same treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed metastatic or
             unresectable gastric or esophageal adenocarcinoma, including GEJ adenocarcinoma which
             will 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 (i.e. positron emission tomography [PET]
             scan or magnetic resonance imaging [MRI] in addition to the computed tomography [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 > or = 20 mm with conventional
             techniques, or > 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 - see section 12.1.1 of protocol for further details.

          -  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, or bevacizumab or any other novel
             biologic anti-angiogenic agent.

          -  Age 18 years or older.

          -  Karnofsky performance status > or = 70% (ECOG performance status 0-1).

          -  Peripheral neuropathy < or = grade 1

          -  Hematologic (minimal values):

               -  White blood cell count > or = 3000/mm3

               -  Absolute neutrophil count > or = 1500 cells/mm3

               -  Hemoglobin > or = 9.0 g/dl

               -  Platelet count > or = 100,000/mm3

          -  Hepatic (minimal values):

               -  Total bilirubin < or = to upper limit of normal (ULN)

               -  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. AST and ALT and alkaline phosphatase should be no more than 1-1.5 times
                  the upper limit of normal.

          -  Kidney function (minimal values):

               -  Serum creatinine < or = 1.5 mg/dl

               -  Urinalysis < 2+ proteinuria; urine protein (mg/dl)/urine creatinine (mg/dl) ratio
                  (Up/c) < 1.0

          -  The patient has a PT (INR) < or = 1.5 and a PTT < or = 3 seconds above the upper
             limits of normal if the patient is not on anticoagulation therapy. If a patient is on
             full-dose anticoagulants, the following criteria should be met for enrollment:

               1. 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.

               2. 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 must 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.

        Exclusion Criteria:

          -  Patients who have received previous chemotherapy for the treatment of metastatic or
             unresectable gastric, GEJ, or esophageal 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 bevacizumab, 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.

          -  Minor surgical procedure such as fine needle aspiration, core biopsy, laparoscopy, or
             mediport placement within 7 days prior to initiating treatment.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to day 0

          -  Anticipation of need for major surgical procedure during the course of the study.

          -  Pregnant (positive pregnancy test) or breast feeding.

          -  Urine protein:creatinine (Up/c) ratio > or = 1.0 at screening

          -  History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess
             within 6 months prior to the initiation of treatment.

          -  Serious, non-healing wound, ulcer, or bone fracture.

          -  Blood pressure > 150/100 mmHg

          -  Significant cardiac disease 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 the investigator's opinion,
             that makes the patient unstable to participate in a clinical trial.