FOLFOX Plus Regorafenib in Patients With Unresectable or Metastatic Esophagogastric Cancer
Condition: Esophageal Cancer; Gastric Cancer
Intervention: Regorafenib; 5-Fluorouracil; Leucovorin; Oxaliplatin
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BAY 73-4506 (REGORAFENIB); FLUOROURACIL; LEUCOVORIN; OXALIPLATIN

Summary:

      The purpose of this study is to evaluate the effects, good and/or bad, of the drug
      regorafenib with chemotherapy regime (FOLFOX). This is a a Phase II trial that will study if
      this new treatment is effective and safe in patients with esophagus and stomach cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must have histologically or cytologically confirmed metastatic or unresectable
             esophageal, gastroesophageal junction or gastric adenocarcinoma.

          -  Patient must have disease that can be evaluated radiographically. This may be
             measurable disease or non-measurable disease. Minimum indicator lesion size = 10 mm by
             helical CT or = 20 mm by conventional techniques. Pathological nodes must be = 15 mm
             by the short axis to be considered measurable.

          -  Subject must be able to swallow and retain oral medication

          -  Age 18 years or older.

          -  Karnofsky performance status > or = to 70%

          -  Peripheral neuropathy ≤ grade 1

          -  Hematologic (minimal values) White blood cell count > or = to 3000/mm3© Absolute
             neutrophil count > 1500 cells/ mm3 Hemoglobin > or = to 8.0 g/dl Platelet count > or =
             to 90,000 / mm3 Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5
             x ULN for subjects with liver involvement of their cancer)

          -  Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement
             of their cancer). 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.

          -  Serum creatinine ≤ 1.5 x the ULN

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of study drug. Post-menopausal women (defined as no
             menses for at least 1 year) and surgically sterilized women are not required to
             undergo a pregnancy test..

          -  Patients with prior deep vein thrombosis (DVT) or pulmonary embolism (PE) currently on
             an stable anticoagulation regimen with low molecular weight heparin (LMWH) or
             rivaroxaban will be permitted.

        Exclusion Criteria:

          -  Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm
             Hg on repeated measurement) despite optimal medical management.

          -  Active or clinically significant cardiac disease including:

          -  Congestive heart failure - New York Heart Association (NYHA) > Class II.

          -  Active coronary artery disease.

          -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
             digoxin.

          -  Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before
             randomization, or myocardial infarction within 6 months before randomization.

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Any hemorrhage or bleeding event ≥ NCI CTCAE version 4.0 Grade 3 within 4 weeks prior
             to start of study medication.

          -  Unwillingness to give written informed consent, unwillingness to participate, or
             inability to comply with the protocol for the duration of the study.

          -  Active hepatitis B infection, active hepatitis C infection or known HIV carrier.

          -  Patient may not have received 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.

          -  Patient may not have received prior 5-Fluorouracil, Leucovorin, Oxaliplatin or
             regorafenib. Patient may have received prior radiosensitizing doses of 5Fu if more
             than 6 months have elapsed between the end of adjuvant therapy and registration.

          -  Patient may not have had major surgical procedure within 4 weeks of registration.

          -  Patient may not have had radiation within 2 weeks of registration.