Regorafenib With Low-dose Chemotherapies and Aspirin Followed by Standard Chemotherapies in Metastatic Colorectal Cancer

Recruiting now · Phase 2/Phase 3

Conditions studied: Metastatic Colorectal Cancer

In brief

This study evaluates the interest of regorafenib in combination of metronomic chemotherapies and low-dose aspirin as a 2 months induction therapy before chemotherapy initiation in the second-line metastatic colorectal carcinoma

Key facts

Study ID

NCT05462613

Run by

Centre Hospitalier Universitaire de Besancon

People needed

446

Starts

2023-05-09

Expected to finish

2030-11-01

Last updated by the study team

2024-12-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients with histologically proven metastatic colorectal cancer in progression after a first line of chemotherapy +/- targeted therapy
• Patients must have been treated for their metastatic disease with one of the following regimens as first-line therapy:
• FOLFOX (Oxaliplatine, 5-Fluoro-uracil)
• FOLFIRI (Irinotecan, 5-Fluoro-uracil)
• FOLFIRINOX (Irinotecan, oxaplipatin, 5-Fluoro-uracil) or FOLFOXIRI (irinotecan, oxaliplatin, 5-Fluoro-uracil)
• FOLFOX and anti-VEGFA (bevacizumab only)
• FOLFIRI and anti-VEGFA (bevacizumab only)
• FOLFIRINOX or FOLFOXIRI and anti-VEGFA (bevacizumab only)
• FOLFOX and anti-EGFR (Epiderman Growth Factor Recepto)
• FOLFIRI and anti-EGFR
• FOLFIRINOX or FOLFOXIRI and anti-EGFR
• Of note, a chemotherapy prescribed for metastases occurring within six months after the end of an adjuvant chemotherapy are considered as a second line of therapy.
• Patients should have a history of resistance to first line chemotherapy defined by:
• Disease progression during the first line of their metastatic disease, less than 3 months after the last exposition to chemotherapy (even a chemotherapy regimen mentioned above or a 5-Fluoro-uracil-based maintenance therapy).
• Disease relapse within 6 months after the end of an adjuvant FOLFOX based chemotherapy.
• Disease relapse within 6 months after the surgical resection of metastases following a first line of chemotherapy.
• Life expectancy of at least 3 months
• Female or male with age ≥18 years old
• Performance status Eastern Cooperative Oncology Group World Health Organization (ECOG-WHO) ≤1 (Appendix 1),
• Measurable disease defined according to RECIST v1.1 (scanner or MRI)
• Molecular status: patients eligible should have microsatellite-stable (MSS) status, absence of BRAF V600E (B(Raf gene, val600-to-glu) mutation and a known RAS (Retrovirus Associated Sequences) status.
• Adequate bone marrow, liver and renal functions.
• Haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L
• Total serum bilirubin ≤ 1.5 times upper normal value (ULN), serum alkaline phosphatase < 5 times ULN, aminotransferases (AST/ALT) ≤ 3 × ULN in absence of hepatic metastasis or ≤ 5 if presence of hepatic lesions
• Cockcroft glomerular filtration rate > 50 ml/min

You may not qualify if…

• 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. Patients might be included at least 21 days following the last investigational agent administration.
• 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,
• 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,
• Previous exposure to regorafenib,
• Previous exposure to other anti-angiogenic treatment than bevacizumab,
• Complete deficit in dihydropyrimidine dehydrogenase (DPD),
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication,
• Pregnant or breast-feeding subjects,
• Congestive Heart Failure ≥ New York Heart Association (NYHA) class 2, unstable angina (anginal symptomatology at rest),
• 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 >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),
• Ongoing infection >grade 2 CTCAE V5 (Appendix 6 ),
• Known History of human immunodeficiency virus (HIV) infection,
• Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy,
• Subjects with seizure disorder requiring medication,
• History of organ allograft,
• Subjects with evidence or history of any bleeding diathesis, irrespective of severity,
• Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication,
• Serious, Non-healing wound, active ulcer or untreated bone fracture,
• History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to inclusion,

Where it is running

• CHU de Besançon — Besançon, France (enrolling)
• Hôpital la Pitié-Salpétrière — Paris, France (enrolling)
• Hôpital Saint antoine — Paris, France (enrolling)
• Institut Mutualiste Montsouris — Paris, France (enrolling)
• CHU de Reims - Hôpital Robert Debré — Reims, France (enrolling)
• Hôpital Henri Mondor — Créteil, France (enrolling)
• Centre Georges François Leclerc — Dijon, France (enrolling)
• Hôpital Privé Jean Mermoz — Lyon, France (enrolling)
• Hôpital Nord Franche Comté — Montbéliard, France (enrolling)
• CHU Montpellier — Montpellier, France (enrolling)
• Groupe hospitalier de la région de Mulhouse et Sud Alsace — Mulhouse, France (enrolling)
• Hôpital Européen Georges Pompidou — Paris, France (enrolling)
• CHU Estain — Clermont-Ferrand, France
• Centre Antoine Lacassagne — Nice, France
• Hôpital FOCH — Suresnes, France
• Centre Léon Bérard — Lyon, France

Full record on ClinicalTrials.gov

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