Regorafenib Second Line Treatment of Metastatic or Advanced Upper GI Cancers
Condition: Upper GI Cancer
MeSH terms: Gastrointestinal Neoplasms
Intervention: regorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Regorafenib as a Second Line Single Agent in the Treatment of Metastatic or Advanced
      Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological diagnosis of metastatic or locally advanced inoperable adenocarcinoma of
             the esophagus, gastroesophageal junction or stomach.

          -  Patients must show signs of progression during or less than 4 months after being
             treated with a first line therapy for their metastatic or locally advanced inoperable
             cancer.

          -  Patients must have measureable disease at screening by Response Evaluation Criteria
             for Solid Tumors 1.1 criteria

          -  Age greater than or equal to 18 years.

          -  Eastern Cooperative Oncology Group Performance Status 0-1

          -  Subjects must be able to understand and be willing to sign the written informed
             consent form. A signed informed consent form must be appropriately obtained prior to
             the conduct of any trial-specific procedure.

          -  All acute toxic effects of any prior treatment have resolved to National Cancer
             Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 1 or less
             at the time of signing the Informed Consent Form. Alopecia (any grade) and peripheral
             neuropathy less than grade 2 is allowed.

          -  Adequate bone marrow, liver and liver function as assessed by laboratory requirement

          -  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.

          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the informed consent form until at least 3
             months after the last dose of study drug. Highly effective contraception must be used
             (male condom with spermicidal, diaphragm with spermicidal, intra-uterine device) by
             both sexes.

          -  Subject must be able to swallow and retain oral medication.

        Exclusion Criteria:

          -  Prior use of regorafenib

          -  Uncontrolled hypertension (systolic pressure greater than 140 mm Hg or diastolic
             pressure greater than 90 mm Hg National Cancer Institute Common Terminology Criteria
             for Adverse Events version 4.0 on repeated measurement) despite optimal medical
             management.

          -  Active or clinically significant cardiac disease including:

          -  Congestive heart failure - New York Heart Association greater than Class 2.

          -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers.

          -  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 greater than or equal to National Cancer Institute
             Common Terminology Criteria for Adverse Events Grade 3 within 4 weeks prior to start
             of study medication.

          -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
             accident (including transient ischemic attacks) deep vein thrombosis or pulmonary
             embolism within 6 months of start of study treatment

          -  Subjects with any previously untreated or concurrent cancer that is distinct in
             primary site or histology except cervical cancer in-situ, treated basal cell
             carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was
             curatively treated and without evidence of disease for more than 3 years before
             randomization are allowed. All cancer treatments must be completed at least 3 years
             prior to start of study treatment.

          -  Patients with severe hepatic impairment (Child-Pugh Class C)

          -  Known history of human immunodeficiency virus infection or current chronic or active
             hepatitis B or C infection requiring treatment with antiviral therapy.

          -  Patients requiring intravenous antiviral or intravenous antibiotic treatment for
             ongoing infections

          -  Symptomatic metastatic brain or meningeal tumors.

          -  Presence of a non-healing wound, non-healing skin ulcer, or bone fracture.

          -  Patient's with a history of kidney disease or persistent proteinuria must have less
             than Grade 3 proteinuria per NCI CTCAE v4.0 at screening. If a patient has a history
             of kidney disease or persistent proteinuria, a urine protein test will be performed on
             a random urine sample. If the result is normal then no additional testing is required.
             If the result is abnormal, a 24 hour urine will be collected to determine if
             proteinuria is less than Grade 3.

          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed
             consent.

          -  Pleural effusion or ascites that causes respiratory compromise (greater than or equal
             to National Cancer Institute Common Terminology Criteria for Adverse Events version
             4.0 Grade 2 dyspnea). Patients may undergo thoracentesis and paracentesis to improve
             symptoms prior to enrollment.

          -  History of organ allograft (including corneal transplant).

          -  Known or suspected grade 3 allergy or hypersensitivity to any of the study drugs,
             study drug classes, or excipients of the formulations given during the course of this
             trial.

          -  Any malabsorption condition that in the opinion of the investigator would
             significantly impact drug absorption.

          -  Women who are pregnant or breast-feeding.

          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for
             trial participation.

          -  Substance abuse, medical, psychological or social conditions that in the opinion of
             the investigator may interfere with the subject's participation in the study or
             evaluation of the study results.

          -  Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
             immunotherapy, biologic therapy, or tumor embolization) within 28 days of starting
             study treatment. Palliative radiation is allowed.

          -  Concurrent use of another investigational drug or device during, or within 3 weeks of
             starting study treatment.

          -  Concurrent use of strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine,
             phenobarbital, and St. John's Wort)

          -  Concurrent use with strong inhibitors of CYP3A4 (e.g. clarithromycin, grapefruit
             juice, itraconazole, ketoconazole, nefazadone, posaconazole, telithromycin, and
             voriconazole)

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks
             before start of study medication.