Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer
Condition: HER2 Positive Esophagogastric Cancer
Intervention: 5-Fluorouracil; Oxaliplatin; Lapatinib; Radiation Therapy
Intervention description: 5-FU, 225 mg/m2 IVCI, during XRT.; Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.; Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion; Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6
Intervention MeSH terms: Fluorouracil; Oxaliplatin; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Esophagogastric Adenocarcinoma; 5-Fluorouracil; Oxaliplatin; Lapatinib; Radiation Therapy; Surgery

Summary:

      With improvements in response rate and survival seen for HER2 positive patients treated with
      HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant setting
      to increase antitumor effect shows promise. Patients with previously untreated localized HER2
      positive esophageal, GE junction and gastric adenocarcinomas will be enrolled. Patients
      meeting all inclusion/exclusion criteria will receive neoadjuvant treatment with concurrent
      chemotherapy and radiation therapy beginning on day 1 of treatment. During the lead-in safety
      portion, the optimal dose of lapatinib will be determined.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed Stage I, II, or III adenocarcinoma of the esophagus (lower
             ⅓), GE junction, or gastric cardia.

          -  Clinical stage I, II, or III as assessed by required baseline staging. In addition,
             patients with celiac node involvement (stage IVa) are eligible.

          -  Patients must be surgical candidates based on stage and location of disease as well as
             other medical conditions and risk factors.

          -  Positive HER2 status (overexpression and/or amplification of HER2 in primary tumor) as
             defined by FISH (HER2 FISH positivity).

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.

          -  Patient must be able to swallow and absorb oral medication.

          -  Patients must have an indwelling central venous access catheter.

          -  Adequate hematologic, renal, and hepatic function:

          -  Known brain or leptomeningeal metastases.

          -  Male patients willing to use adequate contraceptive measures.

          -  Female patients who are not of child-bearing potential, and female patients of
             child-bearing potential who agree to use adequate contraceptive measures, who are not
             breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours
             prior to start of treatment.

          -  Life expectancy ≥ 12 weeks.

          -  Age ≥18 years of age.

          -  Willingness and ability to comply with trial and follow-up procedures.

          -  Ability to understand the nature of this trial and give written informed consent.

        Exclusion Criteria:

          -  Patients with evidence of distant metastases are ineligible, as are patients who are
             not potential surgical candidates based on location or extent of local disease.
             Patients with celiac nodal disease (Stage IVa) will be allowed on study.

          -  Previous anti-cancer treatment for esophageal, GE junction, or gastric cancer.

          -  Any other investigational agents within the 28 days prior to day 1 of the study.

          -  Known active hepatic or biliary disease (with exception of patients with Gilbert's
             syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease
             per investigator assessment).

          -  Concurrent treatment with drugs known to be strong inhibitors or inducers of isoenzyme
             CYP3A that cannot be discontinued or switched to different medication prior to
             starting study drug.

          -  Concurrent use of St. John's wort and grapefruit /grapefruit juice ≤7 days prior to
             starting study drug is not allowed.

          -  Ongoing treatment with full-dose warfarin or its equivalent. Prophylactic treatment
             with 1 mg daily of warfarin and/or low molecular weight heparin is allowed.

          -  History of any other disease, physical examination finding, or clinical laboratory
             finding giving reasonable suspicion of a disease or condition that contraindicates the
             use of a novel regimen, or that might affect interpretation of the results of this
             study or render the subject at high-risk for treatment complications.

          -  Active gastrointestinal (GI) disease or other condition that in the opinion of the
             investigator will interfere significantly with the absorption, distribution,
             metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled
             nausea, or vomiting).

          -  Poorly controlled or clinically significant atherosclerotic vascular disease

          -  A serious active infection at the time of treatment, or another serious underlying
             medical condition that would impair the ability of the patient to receive protocol
             treatment.

          -  Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis
             C (HCV).

          -  Presence of other active cancers, or history of treatment for invasive cancer ≤5
             years. Patients with stage I cancer who have received definitive local treatment at
             least 3 years previously, and are considered unlikely to recur are eligible. All
             patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible,
             as are patients with history of non-melanoma skin cancer.

          -  Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.

          -  Inability or unwillingness to comply with study and/or follow-up procedures outlined
             in the protocol.