NCT02651415

Phase II Study of Perindopril and Regorafenib in mCRC

A Phase II Trial of the Effect of Perindopril on HFSR Incidence and Severity in Patients Receiving Regorafenib With Refractory Metastatic Colorectal Carcinoma (mCRC)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: British Columbia Cancer Agency · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The investigators hypothesize that treatment of regorafenib-treated mCRC patients with perindopril may reduce HFSR compared to reported incidence and severity. The investigators also hypothesize that treatment of regorafenib-treated mCRC patients with perindopril will likely reduce hypertension, a known adverse effect of vascular endothelial growth factor/receptor (VEGF/VEGFR) inhibition. According to the 2014 Canadian Cancer Statistics, colorectal cancer is the second most frequently diagnosed cancer in Canadian males and the third most frequently diagnosed cancer in Canadian females, accounting for 13.9% and 11.6% of new diagnoses, respectively. Although mortality rates are declining very slightly, colorectal cancer is the second most frequent cause of cancer deaths in males and the third most frequent cause of cancer death in females, at 12.8% and 11.5% respectively. Metastatic colorectal cancers are generally not curable. Median overall survival for patients with unresectable mCRC who receive best supportive care (BSC) is five to six months. Palliative treatment with systemic chemotherapy is the best option prolonging survival and maintaining quality of life. Patients who are exposed to all active drugs can sometimes extend survival past two years. For many years 5 Fluorouracil (FU) was the only treatment, but the approval of irinotecan, oxaliplatin, fluoropyrimidines, as well as various monoclonal antibodies targeting VEGF and epidermal growth factor receptor (EGFR) growth factors led to the development of a number of different regimens. The ideal combination and sequence of the different agents is still not determined. Recently, Regorafenib has shown efficacy in patients pretreated with all these options in a large phase III trial, where it prolonged overall survival (OS) compared with placebo (Grothey, et al 2013). In addition, the results were confirmed in a smaller randomised trial in the Asian population, with patients being less intensively pre-treated (Li et al, 2014). Therefore, regorafenib is now considered a standard option in pre-treated patients. The intended outcome of successfully and significantly mitigating regorafenib-induced HFSR is that patients will be able to stay on the regorafenib for a longer period to increase efficacy. The hypothesis underlying this trial is that the co-administration of perindopril with regorafenib will mitigate HFSR symptoms. This may not be the case, and if the HFSR is more severe with the addition of perindopril than with regorafenib alone, the study will be discontinued. As a secondary endpoint, hypertension will also be followed.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Regorafenib	Stivarga® will be used as per the marketed indication ("on label"), Coversyl will be used off-label and as such a Clinical Trial Application will be filed with Health Canada. Regorafenib will be administered 160 mg daily for 21 days of a 28 day cycle. Regorafenib will be administered with low fat breakfast, one hour after perindopril. A low fat breakfast as defined by the Stivarga ® (regorafenib) Product Monograph is one that is \<30% fat, \~300-550 calories.
DRUG	Perindopril	COVERSYL® (perindopril erbumine) 4 mg will be administered daily for 21 days of a 28 day cycle. Perindopril will be administered orally, first thing in the morning on an empty stomach.

Timeline

• Start date: 2016-08-01
• Primary completion: 2018-03-01
• Completion: 2018-11-07
• First posted: 2016-01-11
• Last updated: 2019-09-12
• Results posted: 2019-09-12

Locations

1 site across 1 country: Canada