Clinical Trial Radar

Diagnosis of additional malignancy within 2 years prior to the inclusion (exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical and/or bladder cancer),

Current participation in a study of an investigational agent or in the period of exclusion

Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before inclusion in the trial ;

Patient under judicial protection (curators, autorship) and/or deprived of freedom,

Previous exposition to regorafenib or anti-angiogenic treatment other than bevacizumab and aflibercept

Treatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN,

Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks,

Chronic treatment with drug potentially interacting with regorafenib i.e. CYP3A4, CYP2C9 or UGT1A9 (UDP-glucuronosyltransferase 1-9) inductor/inhibitor; Epileptic disorder requiring medication; Recent or concomitant treatment with brivudine,

Complete deficit in dihydropyrimidine dehydrogenase (DPD),

Known hypersensitivity to any of the study drugs, study drug classes or excipient in the formulation:

• History of severe and unexpected reactions to fluoropyrimidine therapy,
• History of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines,
• Mastocytosis, for whom the use of acetylsalicylic acid can cause severe hypersensitivity reactions,

Unresolved toxicity higher than CTCAE (v5) Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neuropathy ≤ Grade 2,

Subject unable to swallow oral medications or any malabsorption condition,

Inadequate organ functions:

• known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition
• Congestive Heart Failure ≥ New York Heart Association (NYHA) class 2,
• Myocardial infarction less than 6 months before start of study drug, unstable angina (anginal symptoms at rest), new-onset angina (begun within the last 3 months), Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted),
• Uncontrolled hypertension (defined by systolic blood pressure ≥ 150 mmHg and/or diastolic pressure ≥ 100 mmHg despite optimal medical management), or history of hypertensive crisis, or hypertensive encephalopathy
• Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea),
• Interstitial lung disease with ongoing signs or symptoms,
• Ongoing infection >grade 2 CTCAE V5,
• Dehydration CTCAE v5 grade ≥1,
• Urinary tract obstruction

Constitutional or acquired hemorrhagic disease:

• Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication,
• History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to inclusion,
• Serious, Non-healing wound, active peptic ulcer or untreated bone fracture,
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication,

Planned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment,

Known History of human immunodeficiency virus (HIV) infection; Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy,

Receipt of yellow fever vaccine within 28 days prior to study,

History of organ allograft,

Pregnant or breast-feeding subjects