Trial Outcomes & Findings for Phase II Study of Perindopril and Regorafenib in mCRC (NCT NCT02651415)

Last Updated: 2019-09-12

Results Overview

The trial will measure the toxicities of HFSR in participants receiving both perindopril and regorafenib using the CTCAE v4.03 criteria. The toxicity of HFSR will be expressed based on the number of participants in the study (N=10) who are experiencing HFSR of all grades.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)

Results posted on

2019-09-12

Participant Flow

Study conducted from August 2016 - November 2018. 12 Patients were enrolled but only 10 were evaluable.

Participant milestones

Participant milestones
Measure	Single Arm Trial All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
Overall Study STARTED	12
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

12 participants were enrolled but only 10 participants were evaluable.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regorafenib and Perindopril n=12 Participants Phase II, open label, single arm trial of patient with refractory metastatic colorectal carcinoma (mCRC) treated with regorafenib (10 mg/day) and perindopril (4 mg/day). There will be no stratification in this study. 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. 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.
Age, Categorical <=18 years	0 Participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Age, Categorical Between 18 and 65 years	6 Participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Age, Categorical >=65 years	4 Participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Age, Continuous	60.65 Years n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Sex: Female, Male Female	5 Participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Sex: Female, Male Male	5 Participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Race/Ethnicity, Customized Asian	5 participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Race/Ethnicity, Customized Black	1 participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Race/Ethnicity, Customized Caucasian	4 participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.
Region of Enrollment Canada	10 participants n=10 Participants • 12 participants were enrolled but only 10 participants were evaluable.

PRIMARY outcome

Timeframe: Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)

Outcome measures

Outcome measures
Measure	Single Arm Trial n=10 Participants All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
Number of Participants That Have Any Grade HFSR Toxicity	7 Participants

SECONDARY outcome

Timeframe: Weekly for the first six weeks while on the study drug, then every second week and during the 30-day follow-up period

All grades of hypertension will be evaluated using CTCAE v4.03, weekly for the first six weeks while they are on the study drug, then every second week and during the 30-day follow-up period (Post therapy).

Outcome measures

Outcome measures
Measure	Single Arm Trial n=10 Participants All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
The Number of Participants That Experienced Any Grade of Hypertension as Assessed by CTCAE v4.03 Criteria When Treated With a Combination of Regorafenib and Perindopril	6 Participants

SECONDARY outcome

Timeframe: At baseline and at D1 of each cycle while on the study drug and during the 30-day follow-up period

All grades of adverse events (including HFSR) will be evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow-up period (Post therapy).

Outcome measures

Outcome measures
Measure	Single Arm Trial n=10 Participants All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
The Number of Participants That Experienced All Grade Toxicities as Assessed by CTCAE v4.03 Criteria When Treated With a Combination of Regorafenib and Perindopril	10 participants

SECONDARY outcome

Timeframe: Up to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)

The number of participants that experienced an HFSR of grade 3 or above as assessed by CTCAE v4.03 criteria when treated with a combination of regorafenib and perindopril.

Outcome measures

Outcome measures
Measure	Single Arm Trial n=10 Participants All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
Number of Participants With Maximal Severity of HFSR as Assessed by CTCAE v4.03 Criteria When Treated With a Combination of Regorafenib and Perindopril	5 Participants

SECONDARY outcome

Timeframe: p to Safety Follow-Up Visit (30 days +/- 7 days after permanently stopping study treatment)

Median time course for participants to develop worst grade 3 HFSR toxicity is defined as the time (days) from start date of study drug to date of first documented grade 3 HFSR toxicity and will be calculated only for patients who had a HFSR toxicity grade 3.

Outcome measures

Outcome measures
Measure	Single Arm Trial n=10 Participants All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
Median Time Course to Development of Worst Grade (Grade 3) HFSR as Assessed by CTCAE v4.03 Criteria When Treated With a Combination of Regorafenib and Perindopril	12 days Interval 9.0 to 83.0

SECONDARY outcome

Timeframe: From start date of study drugs to the date of first documented disease progression or death due to any cause.

Median time (in months) to PFS. PFS is defined as the time from start date of study drugs to the date of first documented disease progression (radiological or clinical) or death due to any cause, if death occurs before progression is documented. PFS will be evaluated based on RECIST v1.1 criteria, 20% progression or any new lesion.

Outcome measures

Outcome measures
Measure	Single Arm Trial n=10 Participants All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
Median Time to Progression Free Survival (PFS)	2.60 Months Interval 1.74 to 3.61

Adverse Events

Single Arm Trial

Serious events: 1 serious events

Other events: 10 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Single Arm Trial n=10 participants at risk All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
Gastrointestinal disorders RUQ Abdominal Pain; Pneumonia	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Malignant Neoplasm, Grade 5	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).

Other adverse events

Other adverse events
Measure	Single Arm Trial n=10 participants at risk All patients in this single-arm trial will receive treatment with regorafenib and perindopril.
Vascular disorders Hypertension	60.0% 6/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Investigations Increased AST	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
General disorders Fatigue	70.0% 7/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Abdominal pain	50.0% 5/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	70.0% 7/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Metabolism and nutrition disorders Anorexia	60.0% 6/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Mucositis oral	60.0% 6/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Diarrhea	50.0% 5/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Musculoskeletal and connective tissue disorders Myalgia	50.0% 5/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Skin and subcutaneous tissue disorders Rash maculo-papular	40.0% 4/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Nausea	40.0% 4/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Constipation	40.0% 4/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Respiratory, thoracic and mediastinal disorders Hoarseness	40.0% 4/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Musculoskeletal and connective tissue disorders Arthralgia	40.0% 4/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Musculoskeletal and connective tissue disorders Pain in extremity	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Infections and infestations Urinary tract infection	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
General disorders Fever	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Skin and subcutaneous tissue disorders Dry skin	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Vomiting	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Ascites	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Nervous system disorders Headache	30.0% 3/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Reproductive system and breast disorders Pelvic pain	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
General disorders Non-cardiac chest pain	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Musculoskeletal and connective tissue disorders Back pain	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Rectal pain	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Gastrointestinal disorders Dysphagia	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
General disorders Localized edema	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Respiratory, thoracic and mediastinal disorders Dyspnea	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Respiratory, thoracic and mediastinal disorders Cough	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Skin and subcutaneous tissue disorders Erythema multiforme	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Psychiatric disorders Insomnia	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Skin and subcutaneous tissue disorders Pruritus	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
General disorders Pain	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
General disorders Chills	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Respiratory, thoracic and mediastinal disorders Epistaxis	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Investigations Weight loss	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Nervous system disorders Paresthesia	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Metabolism and nutrition disorders Hypokalemia	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Investigations Blood bilirubin increased	20.0% 2/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Investigations Alkaline phosphatase increased	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Investigations Lipase increased	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Investigations INR increased	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Renal and urinary disorders Hematuria	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Musculoskeletal and connective tissue disorders Cramps (leg)	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).
Respiratory, thoracic and mediastinal disorders Haemoptysis	10.0% 1/10 • The PARICCA study was conducted from August 2016 to November 2018 and during this time period, adverse event (AE) data were collected. All grades of AE (including HFSR) were evaluated using CTCAE v4.03, at baseline and at D1 of each cycle while they are on the study drug and during the 30-day follow up period (Post therapy).

Additional Information

Dr. Barbara Melosky

BC Cancer

Phone: 604-877-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place