PaTcH Study: A Phase 2 Study of Trametinib and Hydroxychloroquine in Patients With Metastatic Refractory Pancreatic Cancer

Exclusion Criteria

• •1. Persisting toxicity related to prior therapy (CTCAE Grade \> 1); however alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
• •2. Prior treatment with a MEK inhibitor
• •3. Known history of testing positive for Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome.
• •4. Any significant disease that, in the opinion of the investigator, may impair the patient's tolerance of study treatment.
• •5. Patients who are receiving any other investigational agents within 28 days before start of study treatment.
• •6. Prior organ transplantation including allogenic stem-cell transplantation.
• •7. Patients with known central nervous system metastases.
• •8. Active uncontrolled infection, requiring systemic therapy.
• •9. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• •10. Severe left ventricular dysfunction as defined by ejection fraction \< 45%
• •11. Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• •12. Known maculopathy of the eye
• •13. Known history or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
• •14. Screening corrected QT interval by Fridericia (QTcF) \> 500 msec
• •15. Pregnant women and breastfeeding mothers are excluded due to unknown impact on embryos or infants
• •16. Known prior severe hypersensitivity to investigational products or any component in its formulation.
• •17. Concurrent use of medicines known to induce retinal toxicity (e.g. tamoxifen) or QT interval prolonging agents.
• •18. Known congenital or documented acquired QT prolongation.
• •19. Uncorrected hypokalemia and/or hypomagnesemia.