A Phase II Trial of the Effect of Perindopril on HFSR Incidence and Severity in Patients Receiving Regorafenib With Refractory Metastatic Colorectal Carcinoma (mCRC)
The purpose of this study is to find out what effects the combination of regorafenib and perindopril has on hand-foot skin reaction (HFSR), on high blood pressure (hypertension) and on any other types of side-effects and compare it to the published incidence of the side-effects with regorafenib alone. This research is being done in an attempt to reduce the side-effects associated with regorafenib.
∙ Patients with metastatic colorectal cancer (mCRC) who have progressed on/after, or are intolerant to all approved drugs for CRC and are eligible for regorafenib.
∙ In order to be eligible, all inclusion criteria must be met.
∙ A patient must:
• Understand, be willing to give consent, and sign a written informed consent form (ICF) prior to undergoing any study-specific procedure
• Be male or female and ≥ 18 years of age
• Histological or cytological documentation of adenocarcinoma of the colon or rectum.
• Patients with metastatic colorectal cancer (Stage IV) previously treated with fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy.
• Progression during or within 3 months following the last administration of approved standard therapies, or have experienced intolerance to previous therapy.
• Metastatic CRC patients with measurable or non-measurable disease
• Life expectancy of at least 3 months
• Have an Eastern Cooperative Oncology Group performance status of 0 or 1 (within 14 days prior to the initiation of study treatment)
• Have adequate bone marrow, liver function, and renal function as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment:
‣ Total bilirubin \< 1.5 times the upper limit of normal (ULN)
⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 times the ULN (\< 5 times ULN for patients with liver involvement of their cancer)
⁃ Lipase \< 1.5 times the ULN
⁃ Serum creatinine \< 1.5 times the ULN
⁃ Glomerular filtration rate \> 30 mL/min/1.73 m2 according to the modified diet in renal disease abbreviated formula
⁃ International normalized ratio (INR) of prothrombin time (PT; PT-INR) and partial thromboplastin time (PTT) \< 1.5 times the ULN
⁃ Platelet count \> 100000 /mm3, hemoglobin \> 9 g/dL, absolute neutrophil count \> 1500/mm3.
⁃ Alkaline phosphatase limit ≤ 2.5 times the ULN (\< 5 times ULN for patients with liver involvement of their cancer)
• If female and of childbearing potential, have a NEGATIVE result on a pregnancy test performed a maximum of 7 days before initiation of study treatment.
• If female and of childbearing potential or if male, must agree to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method) 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.