Regorafenib in Subjects With Antiangiogenic-naive and Chemotherapy-refractory Advanced Colorectal Cancer

An Uncontrolled, Open-label Phase IIb Trial of Regorafenib in Subjects With Antiangiogenic-naive and Chemotherapy-refractory Advanced Colorectal Cancer

To determine the efficacy (as measured by progression-free survival [PFS] rate at 8 weeks) of regorafenib in subjects with metastatic colorectal cancer (CRC) whose disease is refractory to standard therapies and who were never exposed to antiangiogenic therapy.

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Regorafenib (Stivarga, BAY73-4506)

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01246000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects ≥18 years of age;
• Histological or cytological confirmation of adenocarcinoma of the colon or/and rectum;
• Subjects with metastatic colorectal cancer (CRC) whose disease progressed or who were intolerant to standard chemotherapy based on fluoropyrimidine, oxaliplatin, irinotecan, and an anti-EGFR therapy if RAS wild-type. This progression must be during or within 4 months following the last administration of standard therapies.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone-marrow, liver, and renal function
• Women of childbearing potential and men must agree to use adequate contraception when sexually active during the study and for at least 8 weeks after the last study drug administration.

Exclusion Criteria:

• Prior treatment with an antiangiogenic agent;
• Congestive heart failure of New York Heart Association (NYHA) class 2 or worse;
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug;
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg despite optimal medical management);
• Ongoing acute or chronic infection (> Grade 2 NCI-CTCAE v 4.03);
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication) events within 6 months of study enrollment. Subjects being treated with low-weight heparin are allowed to participate as long as dose is limited to prophylactic use.
• Any history of or currently known brain metastases (head CT/MRI will be performed during screening period if brain metastases are suspected)
• Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years before study entry, except for curatively treated cervical cancer in situ, in situ ductal breast cancer, non-melanoma skin cancer and superficial bladder tumors;
• Last chemotherapy dose or any other anti-cancer therapy administered in less than 4 weeks from start of study treatment;
• Use of therapeutic anticoagulation;
• Proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (Grade 3, NCI-CTCAE v 4.03) on urinalysis screening result. If there is medical history of proteinuria, previous urinalysis results should be considered and/or performed so at least 2 results separated by at least 2 weeks are available;
• History of interstitial lung disease with ongoing signs and symptoms at the time of informed consent;
• Non-healing wound, non-healing ulcer, or non-healing bone fracture;
• Subjects with evidence or history of any bleeding diathesis, irrespective of severity;
• Any hemorrhage or bleeding event ≥ Grade 3 NCI-CTCAE v 4.03 within 4 weeks prior to the start of study medication;
• Known history of human immunodeficiency virus (HIV) infection;
• History of active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy;
• Pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regorafenib (BAY73-4506); Regorafenib 160 mg orally once a day for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).	Drug: Regorafenib (Stivarga, BAY73-4506); Regorafenib 160 mg orally once a day for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants without disease progression or death at the end of 8 weeks	At week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the date from the first dose of regorafenib until radiologic and/or clear clinical progression or death from any cause, whichever comes first.	Approximately 2 months
Overall Survival (OS)	OS is defined as the date from the first dose of regorafenib until death by any cause.	Approximately 2 months
Overall Response Rate (ORR)	ORR is defined as the proportion of subjects with the best tumor response (confirmed PR or CR) that is achieved during or within 30 days after therapy.	Approximately 2 months
Disease Control Rate (DCR)	DCR is defined as the proportion of subjects who have a best response rating over the whole duration of the study of CR, PR, or SD.	Approximately 2 months
Metabolic response measured by [18F] fluorodeoxyglucose positron emission tomography (FDG PET)		Approximately 2 months
Percentage of participants with grade 1 or higher adverse events, using NCI Common Terminology Criteria for Adverse Events (CTC-AE) Version 4.03		Approximately 2 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Riechelmann RP, Leite LS, Bariani GM, Glasberg J, Rivelli TG, da Fonseca LG, Nebuloni DR, Braghiroli MI, Queiroz MA, Isejima AM, Kappeler C, Kikuchi L, Hoff PM. Regorafenib in Patients with Antiangiogenic-Naive and Chemotherapy-Refractory Advanced Colorectal Cancer: Results from a Phase IIb Trial. Oncologist. 2019 Sep;24(9):1180-1187. doi: 10.1634/theoncologist.2019-0067. Epub 2019 Jun 7.

Helpful Links

• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2015
• Primary Completion (Actual): May 2, 2017
• Study Completion (Actual): December 11, 2017

Study Registration Dates

• First Submitted: June 4, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): November 7, 2018
• Last Update Submitted That Met QC Criteria: November 6, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Colorectal cancer; Regorafenib
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 17217

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No