Regorafenib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction Who Have Completed Chemoradiation Therapy and Surgery
Condition: Adenocarcinoma of the Gastroesophageal Junction; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Intervention: Placebo; Regorafenib
Intervention description: Given PO; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well regorafenib works in treating patients with
      cancer of the esophagus or gastroesophageal junction that has spread from where it started to
      nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery.
      Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological confirmation of node positive (any T stage N1-3) proximal esophageal,
             distal esophagus or gastroesophageal (GE) junction adenocarcinoma (Siewert I, II, or
             III) after completing preoperative chemoradiation and surgery; supporting pathology
             report sufficient for registration; available tumor tissue from endoscopic biopsies
             prior to preoperative chemotherapy (chemo)/radiation therapy (RT), and tumor from
             surgical specimens will be submitted to Academic and Community Cancer Research United
             (ACCRU), but not be required prior registration; Note: if tissue is depleted, patient
             will still be eligible after discussion with the physician

          -  Imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) =< 28 days of
             study registration negative for disease recurrence

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Total bilirubin =< 1.5 x the upper limits of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (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)

          -  Lipase =< 1.5 x the ULN

          -  Serum creatinine =< 1.5 x the ULN

          -  International normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN;
             Note-subjects who are therapeutically treated with an agent such as warfarin or
             heparin will be allowed to participate provided that their medication dose and INR/PTT
             are stable; close monitoring (day 1 of each cycle) is mandatory; if either of these
             values is above the therapeutic range, the doses should be modified and the
             assessments should be repeated weekly until they are stable

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Provide informed written consent

          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study)

          -  Able to swallow and retain oral medications and begin therapy within 6 to 12 weeks
             post-surgery

          -  Provide blood samples for the mandatory correlative research purposes

        Exclusion Criteria:

          -  Presence of metastatic or recurrent disease

          -  R1 or R2 resection

          -  Patients who have not recovered from serious adverse events (as determined by treating
             doctor of medicine [MD]) related to surgery

          -  Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm
             Hg on repeated measurement) despite optimal medical management per physician
             discretion

          -  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 < 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 >= National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI CTCAE) version 4 grade 3 =< 4 weeks prior to
             registration

          -  Prior cancers < 3 years, with the exception of in-situ cervical cancer, low grade
             prostate cancer and basal or squamous cell skin cancers

          -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
             accident (including transient ischemic attacks) deep vein thrombosis or pulmonary
             embolism =< 6 months prior to registration

          -  Receiving any medications or substances that are strong or moderate inhibitors of
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of strong or
             moderate inhibitors are prohibited =< 7 days to registration

          -  Receiving any medications or substances that are inducers of CYP3A4; use of inducers
             are prohibited =< 7 days prior to registration