Regorafenib in Combination With Multimodal Metronomic Chemotherapy for Chemo-resistant Metastatic Colorectal Cancers
NCT ID: NCT06425133
Last Updated: 2024-12-24
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
174 participants
INTERVENTIONAL
2024-07-19
2028-09-30
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Regorafenib
• Regorafenib will be administered 3 weeks out of 4 (1 cycle corresponding to 4 weeks) until progression or unacceptable toxicity.
For the first cycle: Regorafenib will be administered according to the "REDOS" schedule week 1: 80 mg regorafenib daily week 2: 120 mg regorafenib daily week 3: 160 mg regorafenib daily week 4 : no regorafenib
For the following cycles: 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.
Blood sample
Blood sample for plasma collection, Blood sample for ctDNA (circulating tumoral DNA) collection
Quality of life questionnaires
EORTC QLQ-C30 questionnaire (Quality of life questionnaire Cancer 30) CR29 questionnaire (Colo-rectal cancer 29) EQ-5D5L questionnaire (EuroQol-5 Dimensions, 5 levels): repeated measures at baseline, M2, M4, M6, M8, M10, M12 and during the end of treatment visit and during the follow-up
Biopsy
Fresh tumor biopsy at baseline and week 8
Regorafenib
For the first cycle: Regorafenib will be administered according to the "REDOS" schedule: week 1: 80 mg regorafenib daily week 2: 120 mg regorafenib daily week 3: 160 mg regorafenib daily week 4 : OFF. For the following cycles: 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.
Regorafenib+ metronomic chemotherapy + aspirin
• Regorafenib will be administered 3 weeks out of 4 (1 cycle corresponding to 4 weeks) until progression or unacceptable toxicity.
For the first cycle: Regorafenib will be administered according to the "REDOS" schedule: week 1: 80 mg daily week 2: 120 mg daily week 3: 160 mg daily week 4 : OFF. For the following cycles: 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 chemotherapy will be administrated as following:Cyclophosphamide: 50 mg per os, daily, for 6 months,Capecitabine: 625mg/m²/orally twice daily, for 6 months.
* Low-dose Aspirin: 75 mg orally, daily, until progression.
Blood sample
Blood sample for plasma collection, Blood sample for ctDNA (circulating tumoral DNA) collection
Quality of life questionnaires
EORTC QLQ-C30 questionnaire (Quality of life questionnaire Cancer 30) CR29 questionnaire (Colo-rectal cancer 29) EQ-5D5L questionnaire (EuroQol-5 Dimensions, 5 levels): repeated measures at baseline, M2, M4, M6, M8, M10, M12 and during the end of treatment visit and during the follow-up
Biopsy
Fresh tumor biopsy at baseline and week 8
Regorafenib + metronomic chemotherapy
• Regorafenib will be administered 3 weeks out of 4 (1 cycle corresponding to 4 weeks) until progression or unacceptable toxicity.
For the first cycle: Regorafenib will be administered according to the "REDOS" schedule: week 1: 80 mg regorafenib daily week 2: 120 mg regorafenib daily week 3: 160 mg regorafenib daily week 4 : OFF. For the following cycles: 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 chemotherapy will be administrated as following:Cyclophosphamide: 50 mg per os, daily, for 6 months,Capecitabine: 625mg/m²/orally twice daily, for 6 months.
* Low-dose Aspirin: 75 mg orally, daily, until progression.
Interventions
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Blood sample
Blood sample for plasma collection, Blood sample for ctDNA (circulating tumoral DNA) collection
Quality of life questionnaires
EORTC QLQ-C30 questionnaire (Quality of life questionnaire Cancer 30) CR29 questionnaire (Colo-rectal cancer 29) EQ-5D5L questionnaire (EuroQol-5 Dimensions, 5 levels): repeated measures at baseline, M2, M4, M6, M8, M10, M12 and during the end of treatment visit and during the follow-up
Biopsy
Fresh tumor biopsy at baseline and week 8
Regorafenib
For the first cycle: Regorafenib will be administered according to the "REDOS" schedule: week 1: 80 mg regorafenib daily week 2: 120 mg regorafenib daily week 3: 160 mg regorafenib daily week 4 : OFF. For the following cycles: 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.
Regorafenib + metronomic chemotherapy
• Regorafenib will be administered 3 weeks out of 4 (1 cycle corresponding to 4 weeks) until progression or unacceptable toxicity.
For the first cycle: Regorafenib will be administered according to the "REDOS" schedule: week 1: 80 mg regorafenib daily week 2: 120 mg regorafenib daily week 3: 160 mg regorafenib daily week 4 : OFF. For the following cycles: 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 chemotherapy will be administrated as following:Cyclophosphamide: 50 mg per os, daily, for 6 months,Capecitabine: 625mg/m²/orally twice daily, for 6 months.
* Low-dose Aspirin: 75 mg orally, daily, until progression.
Eligibility Criteria
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Inclusion Criteria
2. Life expectancy of at least 3 months
3. Female or male with age \>18 years old
4. Performance status = 0 or 1 (Annex 1)
5. Measurable disease defined according to RECIST v1.1 guidelines (scanner or MRI)
6. Adequate bone marrow, liver and renal functions.
1. Haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L
2. 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
3. Cockcroft glomerular filtration rate \> 50 ml/min
4. Proteinuria \<2+ (dipstick urinalysis) or ≤1g/24hour
7. No contraindication to Iodine contrast media injection during CT
8. For female patients of childbearing potential, negative pregnancy test within 14 days before starting the study drug. Men and women are required to use adequate birth control during the study (when applicable),
9. Signed and dated informed consent,
10. Ability to comply with the study protocol, in the Investigator's judgment.
11. Registration in a national health care system (CMU included).
Exclusion Criteria
2. Current participation in a study of an investigational agent or in the period of exclusion
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. Previous exposition to regorafenib or anti-angiogenic treatment other than bevacizumab and aflibercept
6. Treatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN,
7. Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks,
8. 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,
9. Complete deficit in dihydropyrimidine dehydrogenase (DPD),
10. 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,
11. Unresolved toxicity higher than CTCAE (v5) Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neuropathy ≤ Grade 2,
12. Subject unable to swallow oral medications or any malabsorption condition,
13. 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
14. 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,
15. 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,
16. Known History of human immunodeficiency virus (HIV) infection; Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy,
17. Receipt of yellow fever vaccine within 28 days prior to study,
18. History of organ allograft,
19. Pregnant or breast-feeding subjects
18 Years
ALL
No
Sponsors
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Groupement Interrégional de Recherche Clinique et d'Innovation
OTHER
Centre Hospitalier Universitaire de Besancon
OTHER
Responsible Party
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Locations
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CHU d'Auxerre
Auxerre, , France
Centre Hospitalier Universitaire de Besançon
Besançon, , France
CH de Colmar
Colmar, , France
Centre Georges-François Leclerc (CGFL)
Dijon, , France
Hôpital Robert Schuman
Metz, , France
Hôpital Nord Franche-Comté
Montbéliard, , France
CHU de Montpellier
Montpellier, , France
CHU de Reims - Hôpital Robert Debré
Reims, , France
Clinique Privée de Strasbourg
Strasbourg, , France
ICANS
Strasbourg, , France
Countries
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Central Contacts
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Facility Contacts
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Anne VILLING, Dr
Role: primary
Angélique VIENOT, Dr
Role: primary
Marion BOLLIET, Dr
Role: primary
François GHIRINGHELLI, Pr
Role: primary
Theo LEGRAND, Dr
Role: primary
Christophe BORG, Pr
Role: primary
Eric ASSENAT, Dr
Role: primary
Olivier BOUCHE, Dr
Role: primary
Louis-Marie DOURTHE, Dr
Role: primary
Meher BEN ABDELGHANI, Dr
Role: primary
Other Identifiers
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2023/805
Identifier Type: -
Identifier Source: org_study_id