Regorafenib With Low-dose Chemotherapies and Aspirin Followed by Standard Chemotherapies in Metastatic Colorectal Cancer
NCT ID: NCT05462613
Last Updated: 2024-12-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2/PHASE3
446 participants
INTERVENTIONAL
2023-05-09
2030-11-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Experimental
Regorafenib + metronomic Capecitabine + metronomic Cyclophosphamide + low-dose Aspirin followed by second line of chemotherapy (Bevacizumab + FOLFOX or FOLFIRI)
quality of life questionnaires
EORTC QLQ-C30 questionnaire (Quality of life questionnaire- Cancer 30) CR29 questionnaire (Colo-rectal cancer 29) EQ-5D3L questionnaire (EuroQol-5 Dimensions, 3 levels)
Blood sample
Blood sample for plasma collection Blood sample for ctDNA (circulating tumoral DNA) collection
Regorafenib
\- Regorafenib will be administered 3 weeks out of 4 for two months or unacceptable toxicity.
* For the first cycle: regorafenib will be administered according to the "REDOS" schedule (80 mg daily for week 1, 120 mg daily for week 2 and 160 mg daily for the third week of the first cycle).
* For the second cycle: regorafenib will be administered at 160mg in the absence of significant toxicity during cycle 1 or at a 80/120mg daily dose according to toxicity observed with the last dose used in the first cycle.
Metronomic chemotherapies
* Capecitabine: 625mg/m²/orally twice daily continuously during the first two months
* Cyclophosphamide: 50 mg per os, daily, for two months
Aspirin
75 mg orally and daily during two months
Bevacizumab
5 mg/Kg every 2 weeks according to investigator practice, until disease progression or unacceptable toxicity
FOLFIRI or FOLFOX
every 2 weeks according to investigator practice
Control
Second line of chemotherapy (Bevacizumab + FOLFOX or FOLFIRI)
quality of life questionnaires
EORTC QLQ-C30 questionnaire (Quality of life questionnaire- Cancer 30) CR29 questionnaire (Colo-rectal cancer 29) EQ-5D3L questionnaire (EuroQol-5 Dimensions, 3 levels)
Blood sample
Blood sample for plasma collection Blood sample for ctDNA (circulating tumoral DNA) collection
Bevacizumab
5 mg/Kg every 2 weeks according to investigator practice, until disease progression or unacceptable toxicity
FOLFIRI or FOLFOX
every 2 weeks according to investigator practice
Interventions
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quality of life questionnaires
EORTC QLQ-C30 questionnaire (Quality of life questionnaire- Cancer 30) CR29 questionnaire (Colo-rectal cancer 29) EQ-5D3L questionnaire (EuroQol-5 Dimensions, 3 levels)
Blood sample
Blood sample for plasma collection Blood sample for ctDNA (circulating tumoral DNA) collection
Regorafenib
\- Regorafenib will be administered 3 weeks out of 4 for two months or unacceptable toxicity.
* For the first cycle: regorafenib will be administered according to the "REDOS" schedule (80 mg daily for week 1, 120 mg daily for week 2 and 160 mg daily for the third week of the first cycle).
* For the second cycle: regorafenib will be administered at 160mg in the absence of significant toxicity during cycle 1 or at a 80/120mg daily dose according to toxicity observed with the last dose used in the first cycle.
Metronomic chemotherapies
* Capecitabine: 625mg/m²/orally twice daily continuously during the first two months
* Cyclophosphamide: 50 mg per os, daily, for two months
Aspirin
75 mg orally and daily during two months
Bevacizumab
5 mg/Kg every 2 weeks according to investigator practice, until disease progression or unacceptable toxicity
FOLFIRI or FOLFOX
every 2 weeks according to investigator practice
Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
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Centre Hospitalier Universitaire de Besancon
OTHER
Responsible Party
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Locations
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CHU de Besançon
Besançon, , France
CHU Estain
Clermont-Ferrand, , France
Hôpital Henri Mondor
Créteil, , France
Centre Georges François Leclerc
Dijon, , France
Centre Léon Bérard
Lyon, , France
Hôpital Privé Jean Mermoz
Lyon, , France
Hôpital Nord Franche Comté
Montbéliard, , France
CHU Montpellier
Montpellier, , France
Groupe hospitalier de la région de Mulhouse et Sud Alsace
Mulhouse, , France
Centre Antoine Lacassagne
Nice, , France
Hôpital Européen Georges Pompidou
Paris, , France
Hôpital la Pitié-Salpétrière
Paris, , France
Hôpital Saint antoine
Paris, , France
Institut Mutualiste Montsouris
Paris, , France
CHU de Reims - Hôpital Robert Debré
Reims, , France
Hôpital FOCH
Suresnes, , France
Countries
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Central Contacts
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Facility Contacts
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Anéglique VIENOT, MD, PhD
Role: primary
Marine JARY, Dr
Role: primary
Christophe TOURNIGAND
Role: primary
François GHIRINGHELLI, Pr
Role: primary
Christelle DE LA FOUCHARDIERE, Pr
Role: primary
Jérôme DESRAME, Dr
Role: primary
Christophe BORG, Pr
Role: primary
Eric ASSENAT, Pr
Role: primary
Stéphanie HUSSON-WETZEL, Dr
Role: primary
Ludovic EVEQUES, Dr
Role: primary
Claire Gallois, Dr
Role: primary
Jean-Baptiste BACHET
Role: primary
Romain COHEN
Role: primary
Emilie SOULARUE, Dr
Role: primary
Olivier BOUCHE, Dr
Role: primary
Asmahane BENMAZIANE TEILLET
Role: primary
Other Identifiers
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2022/702
Identifier Type: -
Identifier Source: org_study_id