Evaluation of Treatment PERSOnalization Based on Its Therapeutic Monitoring in Patients With Metastatic Colorectal Cancer Treated With REgorafenib

Korábbi kezelés

• \- Prior treatment with regorafenib, and with any prior antiangiogenic inhibitor except bevacizumab
• Systemic cancer therapy with unfinished washout (in general 3 weeks except for example for capecitabin which has a 1 week washout)
• Concomitant treatment with a cytochrome P450 3A4 (CYP3A4) inducer or inhibitor or UGT1A9 inhibitor
• Patients unable to swallow oral medication
• Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to inclusion, 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 \[tumor invades lamina propria\])
• Known history of human immunodeficiency virus (HIV) infection, active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy
• Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), within 6 months before the start of study medication
• Myocardial infarction less than 6 months before the start of study medication
• Any hemorrhage or bleeding event ≥ Grade 3, NCI-CTCAE v 5.0 within 4 weeks prior to the start of study medication
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication
• Unresolved toxicity higher than Grade 1, NCI-CTCAE v 5.0, attributed to any prior therapy/procedure excluding alopecia, anemia, hypothyroidism and oxaliplatin induced neuropathy

Más betegség

• Hypersensitivity to the active substance or to any of the excipients
• Digestive obstruction, chronic inflammatory bowel disease or any malabsorption condition
• Ongoing uncontrolled infection (viral, bacterial or fungal)
• Uncontrolled hypertension (systolic blood pressure \>140 mmHg or diastolic pressure \>90 mmHg despite optimal medical management)
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
• Non-healing wound, ulcer or bone fracture
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Egyéb

• Breastfeeding
• Adults legally protected (judicial protection, guardianship or supervision), person deprived of their liberty

• \- Signed and dated informed consent
• Male or female patients ≥ 18 years-old at time of Informed Consent Form (ICF) signature
• Patients must have a histologically proven metastatic colorectal cancer
• Patients who have previously been treated with standard therapy including a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF (bevacizumab or aflibercept) and an anti-EGFR (cetuximab or panitumumab) for patients who had a RAS wild-type tumor
• In mCRC with MSI-H, the patient must have received immunotherapy. For mCRC with BRAF mutation, the patient should have received a BRAF inhibitor if eligible.
• ECOG PS = 0 or 1
• Imaging target greater than one cm must be visible on CT
• Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the pre-therapeutic check-up performed within 7 days before regorafenib initiation: Normal organ functions as defined below :
  • Absolute neutrophil count ≥ 1.3 Giga/L
  • Platelets \> 100 Giga/L
  • Hemoglobin ≥ 9 g/dL
  • Serum creatinine ≤ 1.5 x ULN (Upper Limit of Normal) or Glomerular filtration rate (GFR) ≥30 ml/min/1.73m2 according to the modified Diet in Renal Disease (MDRD) or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) abbreviated formula
  • AST and ALT ≤3 x ULN (≤5.0 × ULN for patients with liver involvement of their cancer)
  • Total Bilirubin ≤2 X ULN
  • Alkaline phosphatase ≤3 x ULN (≤5 x ULN in patient with liver involvement of their cancer and/or with bone metastases). If Alkaline phosphatase \> 3 ULN (or \>5 ULN in patient with liver involvement of their cancer and/or with bone metastases), hepatic isoenzymes 5-nucleotidase or GGT tests must be performed; hepatic isoenzymes 5-nucleotidase must be within the normal range and/or GGT \< 3 x ULN
  • No argument for acute pancreatitis within 3 months before the start of study medication
  • No proteinuria: Spot urine ≥ 1+ protein will require a 24-hour urine collection that must show total protein excretion \<1000 mg/24 hours
• INR/PTT ≤1.5 x ULN
• Patient who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. For patients treated with VKA, close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
• Women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy
• Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days prior randomization
• Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
• Patients affiliated to the Social Security System