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

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Regorafenib (Stivarga, BAY73-4506)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, Regorafenib