Regorafenib in Combination With Paclitaxel in Advanced Oesophagogastric Carcinoma

Inclusion Criteria:

* Patient must understand, be willing to give consent, and sign a written informed consent form prior to undergoing any study-specific procedure
* Male or female and ≥ 18 years of age
* Metastatic or non-resectable adeno- or squamous-cell carcinoma of the stomach or oesophagus who failed on first line cytotoxic treatment with a fluoropyrimidine and platinum compound
* Tumor accessible for repeated biopsies
* Measurable or evaluable disease
* Life expectancy of at least 12 weeks
* Eastern Cooperative Oncology Group performance status of 0 or 1
* Have adequate bone marrow, liver function, and renal function as measured by pre-specified laboratory assessments conducted within 7 days prior to the start of study treatment
* If female and of childbearing potential, have a NEGATIVE result on a pregnancy test performed a maximum of 7 days before start of study treatment
* If female and of childbearing potential or if male, must agree to use adequate contraception based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until 6 months after the last dose of study drug.

Exclusion Criteria:

* Prior treatment with regorafenib
* Contra-indications for repeated biopsies
* Dementia or altered mental status that would prohibit the understanding and giving of informed consent
* Inadequate caloric- and/or fluid intake.
* Pre-existing motor or sensory neurotoxicity greater than WHO grade 1
* Have unresolved toxicity higher than National Cancer Institute-Common Terminology for Adverse Events version 4.0 (NCI-CTCAE v 4.0) Grade 1 attributed to any prior therapy/procedure, excluding alopecia.
* Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
* If female and of childbearing potential, be engaged in breast feeding
* Be unable to swallow oral tablets
* Have congestive heart failure classified as New York Heart Association Class 2 or higher
* Have had unstable angina or new-onset angina ≤ 3 months prior to screening
* Have had a myocardial infarction ≤ 6 months prior to start of study treatment
* Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
* Have uncontrolled hypertension despite optimal medical management
* Have pheochromocytoma
* Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 3 months prior to the initiation of study treatment
* Have an ongoing infection ≥ Grade 2 (NCI-CTCAE v 4.0)
* Have a known history of human immunodeficiency virus infection
* Have either active hepatitis B or C or chronic hepatitis B or C requiring treatment
* Have a seizure disorder requiring medication
* Have currently suspected brain metastases
* Have a history of organ allograft
* Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity
* Have had a hemorrhage or a bleeding event \> Grade 3 ( NCI-CTCAE v 4.0) within 4 weeks prior to the start of study treatment
* Have a non-healing wound, ulcer, or bone fracture
* Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained
* Have any other serious illness or medical condition that could jeopardize the safety of the patient
* Have an unstable illness or medical condition that could jeopardize the safety of the patient and/or his/her compliance
* Have a substance abuse, medical, psychological, or social condition that may interfere with participation in the study or evaluation of the study results
* Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
* Have any malabsorption condition
* Using and unable to stop medication that are prohibited due to interaction
* Unwilling to stop pommelos, citrus fruit and herbal medicine inducing or inhibiting the CYP system