Combination Chemotherapy With or Without Vismodegib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer
Condition: Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms
Intervention: oxaliplatin; leucovorin calcium; fluorouracil; placebo; vismodegib; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Given PO; Given PO; Correlative studies
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies combination chemotherapy when given together with
      vismodegib to see how well it works compared with combination chemotherapy without vismodegib
      in treating patients with advanced stomach cancer or gastroesophageal junction cancer. Drugs
      used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in
      different ways to stop the growth of tumor cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving more than one drug
      (combination chemotherapy) may kill more tumor cells. Vismodegib may stop the growth of
      stomach or gastroesophageal junction cancer by blocking the growth of new blood vessels
      necessary for tumor growth. It is not yet known whether combination chemotherapy is more
      effective when given with or without vismodegib in treating stomach cancer and
      gastroesophageal junction cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed gastric or
             gastroesophageal junction (GEJ) adenocarcinoma not amenable to surgical resection

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT)
             scan

          -  No prior chemotherapy for advanced disease; patients may have receive adjuvant
             chemotherapy or chemoradiation if > 6 months has elapsed since completion of treatment

          -  Life expectancy of greater than 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 70%)

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 1.5 times upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X institutional upper limit of normal (=< 5.0 X institutional upper limit of
             normal with presence of liver metastases)

          -  Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Baseline imaging studies performed =< 28 days of study registration; the treating
             investigator will determine the appropriate imaging studies, which may include CT
             scan, magnetic resonance imaging (MRI), and/or fludeoxyglucose F 18 (FDG)-positron
             emission tomography (PET)/CT

          -  Must be willing to provide blood and tissue samples for research purposes; patient has
             the right to later withdraw consent for research studies and/or tissue specimens

          -  Patients must agree to placement of a central venous catheter for chemotherapy
             administration

          -  Patients must be able to swallow whole capsules

          -  Patients taking medications with narrow therapeutic indices that are metabolized by
             cytochrome P450 (CYP450), including warfarin sodium (Coumadin), must be on a stable,
             therapeutic dose and have close monitoring of their levels

          -  Women of child-bearing potential and men must use two forms of contraception (i.e.,
             barrier contraception and one other method of contraception) at least 4 weeks prior to
             study entry, for the duration of study participation, and for at least 12 months
             post-treatment; should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately

          -  Pregnancy testing: women of childbearing potential are required to have a negative
             serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and
             within 24 hours prior to the first dose of GDC-0449/placebo (serum or urine); a
             pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual
             cycles are regular or every 2 weeks if their cycles are irregular while on study
             within the 24-hour period prior to the administration of GDC-0449/placebo; a positive
             urine test must be confirmed by a serum pregnancy test; prior to dispensing
             GDC-0449/placebo, the investigator must confirm and document the patient's use of two
             contraceptive methods, dates of negative pregnancy test, and confirm the patient's
             understanding of the teratogenic potential of GDC-0449/placebo

          -  Female subjects of childbearing potential are defined as follows:

               -  Patients with regular menses

               -  Patients, after menarche with amenorrhea, irregular cycles, or using a
                  contraceptive method that precludes withdrawal bleeding

               -  Women who have had tubal ligation

          -  Female subjects may be considered to NOT be of childbearing potential for the
             following reasons:

               -  The patient has undergone hysterectomy and/or bilateral oophorectomy.

               -  The patient is post-menopausal defined by amenorrhea for at least 1 year in a
                  woman > 45 years old

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 6 months prior to entering
             the study

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to GDC-0449, 5-fluorouracil or oxaliplatin

          -  GDC-0449 inhibits cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8),
             cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), and cytochrome P450,
             family 2, subfamily C, polypeptide 19 (CYP2C19) drug metabolism enzymes in vitro at
             concentrations that may be clinically relevant; therefore, caution should be exercised
             when dosing GDC-0449 concurrently with medications that are substrates of CYP2C8,
             CYP2C9, and CYP2C19 and have narrow therapeutic windows

          -  Patients with malabsorption syndrome or other condition that would interfere with
             intestinal absorption

          -  Patients unable to swallow whole capsules

          -  Patients with clinically active liver disease, including viral or other hepatitis or
             cirrhosis are ineligible

          -  Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia
             defined as less than the lower limit of normal for the institution, despite adequate
             electrolyte supplementation are excluded from this study

          -  Pre-existing > grade 1 peripheral sensory neuropathy

          -  Previous or concurrent malignancy; exceptions: treated basal cell or squamous cell
             skin cancer, in situ cervical cancer, or lobular carcinoma in situ in one breast; or
             other cancer which the patient has been disease-free ≥5 years

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with GDC-0449

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible