Ph1b Study of Oraxol in Comb. w. Ramucirumab in Patients w. Gastric, Gastro-esophageal, or Esophageal Cancers

Exclusion Criteria

• •Subjects who meet any of the following criteria will be excluded from this study:
• •1. Unresolved toxicity from previous anticancer treatments, including investigational products (subjects must have recovered all unacceptable toxicity to ≤ Grade 1 Common Terminology Criteria for Adverse Events \[CTCAE\] toxicity). This does not extend to symptoms or findings that are attributable to the underlying disease.
• •2. Received investigational products within 14 days or 5 half-lives of the first study dosing day, whichever is longer; subjects receiving biologic agents (eg, monoclonal antibodies) require a 30-day washout period.
• •3. Are currently receiving other medications or radiation intended for the treatment of their malignancy
• •4. Central nervous system metastases, including leptomeningeal involvement
• •5. Women of childbearing potential who are pregnant or breastfeeding
• •6. Currently taking a concomitant medication, other than a premedication, that is:
• •* A strong P-glycoprotein (P-gp) inhibitor or inducer. Subjects who are taking such medications but who are otherwise eligible may be enrolled if they discontinue the medication ≥1 week before dosing
• •* An oral medication with a narrow therapeutic index known to be a P-gp substrate within 24 hours prior to start of dosing in the study
• •* Medications known to be strong inhibitors (gemfibrozil) or inducers (rifampin) of cytochrome P450 (CYP) 2C8 or medications known to be strong CYP3A4 inhibitors (eg, ketoconazole) or inducers (eg, rifampin or St. John's Wort). Subjects who are currently taking such medications but who are otherwise eligible may be enrolled if they discontinue the medication 1 week before dosing and remain off that medication during treatment with Oraxol.
• •7. Use of warfarin. Participants receiving warfarin who are otherwise eligible and who may be appropriately managed with low molecular weight heparin, in the opinion of the Investigator, may be enrolled in the study provided they are switched to low molecular weight heparin at least 7 days prior to receiving study treatment.
• •8. Require chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), chronic antiplatelet therapy, dipyridamole, clopidogrel, or similar agents. Aspirin up to 325 mg per day is allowed.
• •9. Unable to receive iv contrast for required CT scans
• •10. Poorly-controlled hypertension (\>160 mm Hg systolic or \>100 mm Hg diastolic for \>4 weeks) despite standard medical management. Subjects may be rescreened after adjustment of their antihypertensive medication.
• •11. Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy
• •12. Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation
• •13. Grade 3 or 4 GI bleeding within 3 months prior to first dose of protocol therapy
• •14. Arterial thromboembolic event including, but not limited to, myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina within 6 months prior to first dose of protocol therapy
• •15. Deep vein thrombosis (DVT) or pulmonary embolus or any other significant thromboembolic event during the 3 months prior to first dose of protocol therapy
• •16. Child-Pugh Class B or C cirrhosis of the liver or cirrhosis (any degree) and a history of hepatic encephalopathy or a history of ascites resulting from cirrhosis requiring diuretics or paracentesis
• •17. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled diabetes or diabetes with established vascular complications, chronic pulmonary disease requiring oxygen, known bleeding disorders, or any concomitant illness or social situation that would limit compliance with study requirements
• •18. Medical condition that, in the opinion of the investigator, may interfere with oral drug absorption
• •19. Major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy, or elective or major surgery planned to be performed during the course of the clinical trial
• •20. History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity type reaction to Cremophor®, or history of hypersensitivity type reaction to polysorbate 80 or other components of the formulation of Oraxol
• •21. History of developing any condition during prior treatment with ramucirumab for which ramucirumab must be permanently discontinued according to the ramucirumab Investigator's Brochure