Colorectal Neoplasms
Conditions
Keywords
Colorectal cancer, Regorafenib
Brief summary
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.
Interventions
DRUGRegorafenib (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).
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of participants without disease progression or death at the end of 8 weeks | At week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately 2 months | OS is defined as the date from the first dose of regorafenib until death by any cause. |
| Overall Response Rate (ORR) | Approximately 2 months | 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. |
| Progression-Free Survival (PFS) | Approximately 2 months | 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. |
| 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 | — |
| Disease Control Rate (DCR) | Approximately 2 months | 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. |
Countries
Brazil
Outcome results
None listed