Trial Title:
Regorafenib in Combination With Multimodal Metronomic Chemotherapy for Chemo-resistant Metastatic Colorectal Cancers
NCT ID:
NCT06425133
Condition:
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Regorafenib
metronomic chemotherapy
colon cancer
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Blood sample
Description:
Blood sample for plasma collection, Blood sample for ctDNA (circulating tumoral DNA)
collection
Arm group label:
Regorafenib
Arm group label:
Regorafenib+ metronomic chemotherapy + aspirin
Intervention type:
Other
Intervention name:
Quality of life questionnaires
Description:
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
Arm group label:
Regorafenib
Arm group label:
Regorafenib+ metronomic chemotherapy + aspirin
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Fresh tumor biopsy at baseline and week 8
Arm group label:
Regorafenib
Arm group label:
Regorafenib+ metronomic chemotherapy + aspirin
Intervention type:
Drug
Intervention name:
Regorafenib
Description:
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.
Arm group label:
Regorafenib
Intervention type:
Combination Product
Intervention name:
Regorafenib + metronomic chemotherapy
Description:
• 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.
Arm group label:
Regorafenib+ metronomic chemotherapy + aspirin
Summary:
The main objective is to evaluate the impact of a Regorafenib combined with metronomic
chemotherapy (capecitabine and cyclophosphamide) and low-dose aspirin compared to
standard Regorafenib treatment in patients with metastatic colorectal cancer by assessing
progression-free survival.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with histologically proven metastatic colorectal cancer in progression
after previous standard treatments (5FU, CPT11 (Irinotecan), oxaliplatin, anti-VEGF
(vascular endothelial growth factor), trifluridine/tipiracil, anti-EGFR (epidermal
growth factor receptor) therapy if KRAS (Kirsten rat sarcoma) and NRAS WT (wild
type), anti-BRAF therapy if BRAF V600E mutated, and anti-PD1 (Programmed Death-1) if
MSI-H (microsatellite instability) /dMMR (deficient MisMatch Repair) tumor, or not
considered as candidate for these treatments.
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:
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 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU d'Auxerre
Address:
City:
Auxerre
Country:
France
Contact:
Last name:
Anne VILLING, Dr
Facility:
Name:
Centre Hospitalier Universitaire de Besançon
Address:
City:
Besançon
Zip:
25000
Country:
France
Contact:
Last name:
Angélique VIENOT, Dr
Facility:
Name:
CH de Colmar
Address:
City:
Colmar
Country:
France
Contact:
Last name:
Marion BOLLIET, Dr
Facility:
Name:
Centre Georges-François Leclerc (CGFL)
Address:
City:
Dijon
Country:
France
Contact:
Last name:
François GHIRINGHELLI, Pr
Facility:
Name:
Hôpital Robert Schuman
Address:
City:
Metz
Country:
France
Contact:
Last name:
Theo LEGRAND, Dr
Facility:
Name:
Hôpital Nord Franche-Comté
Address:
City:
Montbéliard
Country:
France
Contact:
Last name:
Christophe BORG, Pr
Facility:
Name:
CHU de Montpellier
Address:
City:
Montpellier
Country:
France
Contact:
Last name:
Eric ASSENAT, Dr
Facility:
Name:
CHU de Reims - Hôpital Robert Debré
Address:
City:
Reims
Country:
France
Contact:
Last name:
Olivier BOUCHE, Dr
Facility:
Name:
Clinique Privée de Strasbourg
Address:
City:
Strasbourg
Country:
France
Facility:
Name:
ICANS
Address:
City:
Strasbourg
Country:
France
Contact:
Last name:
Meher BEN ABDELGHANI, Dr
Start date:
September 2024
Completion date:
September 2028
Lead sponsor:
Agency:
Centre Hospitalier Universitaire de Besancon
Agency class:
Other
Collaborator:
Agency:
Groupement Interrégional de Recherche Clinique et d'Innovation
Agency class:
Other
Source:
Centre Hospitalier Universitaire de Besancon
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06425133
