colon cancer Colorectal cancer
Conditions
Interventions
Approximately 690 patients will be randomly assigned (2:1 ratio) to one of the
following treatment groups:
* Regorafenib 160 mg od po. 3 weeks on/1 week off plus BSC
* Placebo plus BSC
Sponsors
Bayer
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Signed informed consent obtained before any study specific procedures. Patients must be able to understand and willing to sign a written informed consent. * Male or female patients > 18 years of age. * Histological or cytological documentation of adenocarcinoma of the colon or rectum. * Progression during or within 3 months following the last administration of approved standard therapies which must include fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab and cetuximab or panitumumab (if KRAS WT), if approved in the respective country. A list of approved standard therapies for the respective countries is in Appendix Error! Reference source not found.. Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed into the study. Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy. * Patients must have measurable or non measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, version 1.1). * Eastern Cooperative Oncology Group (ECOG) Performance Status of * 1. * Life expectancy of at least 3 months. * Women of childbearing potential and men must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the patient how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommend method (or combination of methods) as per standard of care. * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: - Total bilirubin 100000 /mm3, Hemoglobin (Hb) > 9 g/dl, Absolute neutrophil count (ANC) > 1500/mm3 - Alkaline phosphatase limit
Exclusion criteria
Exclusion criteria: * Prior treatment with regorafenib. * Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study. * Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (Non invasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)]. * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication. * Pregnant or breast-feeding patients. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment. * Congestive heart failure > New York Heart Association (NYHA) class 2. * 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 medication. * Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). * Uncontrolled hypertension. (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management). * Patients with phaeochromocytoma. * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication. * Ongoing infection > grade 2 NCI-CTC version 3.0. * Known history of human immunodeficiency virus (HIV) infection. * Known history of chronic hepatitis B or C. * Patients with seizure disorder requiring medication. * Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies) * History of organ allograft * Patients with evidence or history of bleeding diasthesis. Any hemorrhage or bleeding event > CTCAE Grade 3 within 4 weeks of start of study medication. * Non-healing wound, ulcer, or bone fracture. * Renal failure requiring hemo-or peritoneal dialysis. * Dehydration NCI-CTC version 3.0 grade > 1. * Substance abuse, medical, psychological or social conditions that may interfere with the patient*s participation in the study or evaluation of the study results * Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation * Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study. * Interstitial lung disease with ongoing signs and symptoms at the time of informed consent. * Patients unable to swallow oral medications * Persistent proteinuria of CTC Grade 3 or higher (> 3.5 g/24 hrs, measured by urine protein:creatinine ratio on a random urine sample). * Any malabsorption condition * Close affiliation with the investigational site; e.g. a close re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint of this study is Overall survival. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy endpoints of this study are: * Progression free survival * Objective tumor response rate * Disease control rate | — |
Countries
Netherlands
Outcome results
None listed