The present proposal is aimed to evaluate the efficacy and safety of regorafenib as maintenance therapy in increasing the efficacy of the best available therapy for first line treatment fluoropirimidine based chemotherapy , any variant, in combination with either cetuximab or panitumumab) of RAS wild type metastatic colorectal cancer patients. MedDRA version: 18.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant
Conditions
Interventions
Trade Name: Stivarga
Product Name: Stivarga
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Regorafenib
CAS Number: 755037-03-7
Other descriptive name: REGORAFENIB
Concentration unit: mg milli
Sponsors
Department of experimental and clincial medicine "F. Magrassi"
Eligibility
Sex/Gender
All
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 •Histological or cytological documentation of adenocarcinoma of the colon or rectum •Genetic diagnosis of RAS(hot spot mutations KRAS codon 2-3-4 and NRAS at least codon 2-3) wild type tumor . •Previous standard first line treatment defined as fluoropirimidine based chemotherapy (any variant) in combination with either cetuximab or panitumumab for a minimum of 4 months and a maximum of 8 months. •Patients that have achieved either partial response (PR) , complete response (CR) or stable disease (SD) at the completion of the first line treatment after a minimum of 4 months (8 cycles) and a maximum of 8 months (16 cycles) . •Patients with PR/SD must have 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 6months. •Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: o Total bilirubin 100000 /mm3, Hemoglobin (Hb) > 9 g/dl, Absolute neutrophil count (ANC) > 1500/mm3 o Alkaline phosphatase limit =65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: •Prior treatment with regorafenib. •Interruption of the first line treatment for progressive disease or in which progressive disease was diagnosed prior to entry into this study. •Assumption of strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s Wort) (see Section 13.1) •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 > 140 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. •Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiretroviral therapy. •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 diathesis. 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 u
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - Overall survival (OS) - Safety Profile - Biomarker correlative studies;Main Objective: The objective of this study is to evaluate efficacy and safety of regorafenib in the maintenance of the response in patients with metastatic colorectal (CRC) RAS wild type after first line therapy (fluoropirimidine-based plus anti-EGFR Abs). The primary efficacy endpoint of this study is Progression Free Survival (PFS) defined as the time(days) from randomization for maintenance therapy with study drug to PD or death whichever comes first.;Primary end point(s): Progression-free Survival (PFS);Timepoint(s) of evaluation of this end point: 9 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival Safety ;Timepoint(s) of evaluation of this end point: 20 months | — |
Countries
Germany, Spain
Contacts
Public ContactProf. Dr. Fortunato Ciardiello
Department of experimental and clincial medicine "F. Magrassi"
Outcome results
None listed