Informations générales (source: ClinicalTrials.gov)
Induction Regorafenib in Combination With Metronomic Cyclophosphamide, Capecitabine, and Low-dose Aspirin Followed by Chemotherapy in Second Line Metastatic Colorectal Cancer Carcinoma An Open-label Randomized Phase II-III Study
Interventional
Phase 2/Phase 3
Centre Hospitalier Universitaire de Besancon (Voir sur ClinicalTrials)
mai 2023
novembre 2030
05 novembre 2026
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
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| HOPITAL FOCH | Asmahane BENMAZIANE TEILLET | 02/11/2026 18:00:41 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Europeen Georges Pompidou | Contact (sur clinicalTrials) | ||||
| AP-HP - Hôpital Saint Antoine | Contact (sur clinicalTrials) | ||||
| INSTITUT MUTUALISTE MONTSOURIS | Contact (sur clinicalTrials) | ||||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHU de Reims - Hôpital Robert Debré - Reims - France | Contact (sur clinicalTrials) | ||||
| CHU Montpellier - Montpellier - France | Contact (sur clinicalTrials) | ||||
| Groupe hospitalier de la région de Mulhouse et Sud Alsace - Mulhouse - France | Contact (sur clinicalTrials) | ||||
| Hôpital Nord Franche Comté - Montbéliard - France | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - Nice - France | Contact (sur clinicalTrials) | ||||
| Centre Georges François Leclerc - Dijon - France | Contact (sur clinicalTrials) | ||||
| CHU de Besançon - Besançon - France | Contact (sur clinicalTrials) | ||||
| CHU Estain - Clermont-Ferrand - France | Contact (sur clinicalTrials) | ||||
| Hôpital Henri Mondor - Créteil - France | Contact (sur clinicalTrials) | ||||
| Hôpital la Pitié-Salpétrière - Paris - France | Contact (sur clinicalTrials) | ||||
| Hôpital Privé Jean Mermoz - Lyon - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
1. Patients with histologically proven metastatic colorectal cancer in progression
after a first line of chemotherapy +/- targeted therapy
2. 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.
3. 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.
4. Life expectancy of at least 3 months
5. Female or male with age ≥18 years old
6. Performance status Eastern Cooperative Oncology Group World Health Organization
(ECOG-WHO) ≤1 (Appendix 1),
7. Measurable disease defined according to RECIST v1.1 (scanner or MRI)
8. 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.
9. 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
- Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour
10. No contraindication to Iodine contrast media injection during CT
11. For female patients of childbearing potential, negative pregnancy test within 14
days before starting the study drug through at 210 days after the last dose of
regorafenib. Men and women are required to use adequate birth control during the
study (when applicable),
12. Signed and dated informed consent,
13. Ability to comply with the study protocol, in the Investigator's judgment.
14. Registration in a national health care system (CMU included).
Exclusion Criteria:
1. 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),
2. Current participation in a study of an investigational agent. Patients might be
included at least 21 days following the last investigational agent administration.
3. 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;
4. Patient under judicial protection (curators, autorship) and/or deprived of freedom,
5. 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,
6. Previous exposure to regorafenib,
7. Previous exposure to other anti-angiogenic treatment than bevacizumab,
8. Complete deficit in dihydropyrimidine dehydrogenase (DPD),
9. Major surgical procedure, open biopsy or significant traumatic injury within 28 days
before start of study medication,
10. Pregnant or breast-feeding subjects,
11. Congestive Heart Failure ≥ New York Heart Association (NYHA) class 2, unstable
angina (anginal symptomatology at rest),
12. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
months),
13. Myocardial infarction less than 6 months before start of study drug,
14. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are
permitted),
15. 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
16. Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2
dyspnea),
17. Ongoing infection >grade 2 CTCAE V5 (Appendix 6 ),
18. Known History of human immunodeficiency virus (HIV) infection,
19. Active hepatitis B or C or chronic hepatitis B or C requiring treatment with
antiviral therapy,
20. Subjects with seizure disorder requiring medication,
21. History of organ allograft,
22. Subjects with evidence or history of any bleeding diathesis, irrespective of
severity,
23. Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start
of study medication,
24. Serious, Non-healing wound, active ulcer or untreated bone fracture,
25. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI
bleeding within 6 months prior to inclusion,
26. Dehydration CTCAE v4 grade ≥1,
27. Known hypersensitivity to any of the study drugs, study drug classes or excipient in
the formulation,
28. Interstitial lung disease with ongoing signs or symptoms,
29. Persistent proteinuria of CTCAE Grade 3 (>3.5 g/24 hours),
30. Subject unable to swallow oral medications,
31. Any malabsorption condition, unresolved toxicity higher than CTCAE (V4) Grade 1
attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and
oxaliplatin induced neuropathy ≤ Grade 2,
32. Systemic anticancer therapy including cytotoxic therapy, signal transduction
inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks,
33. Treatment with any other investigational medicinal product within 28 days prior to
study entry, EXCEPT for ASPIRIN,
34. Co-administration of drugs potentially interacting with regorafenib i.e. CYP3A4 or
UGT1A9 (UDP-glucuronosyltransferase 1-9) inducers/inhibitors.