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Metastatic Colorectal CancerPhase 2CARENCT06425133

Regorafenib in Combination With Multimodal Metronomic Chemotherapy for Chemo-resistant Metastatic Colorectal Cancers

A Phase 2 study testing Blood sample, Quality of life questionnaires and Biopsy in people with Metastatic Colorectal Cancer, run by Centre Hospitalier Universitaire de Besancon at 13 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Blood sample, Quality of life questionnaires and Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
174 participants
Where
13 sitesFrance
Study dates
19 Jul 2024to Sep 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Life expectancy of at least 3 months
  • Female or male with age >18 years old
  • Performance status = 0 or 1 (Annex 1)
  • Measurable disease defined according to RECIST v1.1 guidelines (scanner or MRI)
  • Adequate bone marrow, liver and renal functions.
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  • 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
  • No contraindication to Iodine contrast media injection during CT
  • 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),
  • Signed and dated informed consent,
  • Ability to comply with the study protocol, in the Investigator's judgment.
  • Registration in a national health care system (CMU included).

Who cannot join

  • 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 or in the period of exclusion
  • 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,
  • Previous exposition to regorafenib or anti-angiogenic treatment other than bevacizumab and aflibercept
  • Treatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN,
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  • Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks,
  • 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,
  • Complete deficit in dihydropyrimidine dehydrogenase (DPD),
  • 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,
  • Unresolved toxicity higher than CTCAE (v5) Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neuropathy ≤ Grade 2,
  • Subject unable to swallow oral medications or any malabsorption condition,
  • 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
  • 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,
  • 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,
  • Known History of human immunodeficiency virus (HIV) infection; Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy,
  • Receipt of yellow fever vaccine within 28 days prior to study,
  • History of organ allograft,
  • Pregnant or breast-feeding subjects

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Angélique VIENOT, Dr contact

+33 370632278

a3vienot@chu-besancon.fr

Christophe BORG, Pr contact

xtoph.borg@gmail.com

13 sites in 1 country

France13 sites, 13 recruiting

  • CHU d'Auxerre

    Auxerre

    Anne VILLING, Dr

    Recruiting

  • Centre Hospitalier Universitaire de Besançon

    Besançon, 25000

    Angélique VIENOT, Dr

    Recruiting

  • Centre Hospitalier William Morey

    Chalon-sur-Saône

    Pierre VERDIER, DR

    Recruiting

  • CH de Colmar

    Colmar

    Marion BOLLIET, Dr

    Recruiting

  • Centre Georges-François Leclerc (CGFL)

    Dijon

    François GHIRINGHELLI, Pr

    Recruiting

  • Hopital Jean Mermoz

    Lyon

    Matthieu SARABI, Dr

    Not yet recruiting

  • Hôpital Robert Schuman

    Metz

    EL DEMERY, Dr

    Recruiting

  • Hôpital Nord Franche-Comté

    Montbéliard

    Christophe BORG, Pr

    Recruiting

  • CHU de Montpellier

    Montpellier

    Eric ASSENAT, Dr

    Recruiting

  • Institut de Cancérologie de Lorraine

    Nancy

    Aurélien LAMBERT, Dr

    Not yet recruiting

  • CHU de Reims - Hôpital Robert Debré

    Reims

    Olivier BOUCHE, Dr

    Recruiting

  • Centre Paul Strauss

    Strasbourg

    Meher BEN ABDELGHANI, Dr

    Recruiting

  • Clinique Privée de Strasbourg

    Strasbourg

    Louis-Marie DOURTHE, Dr

    Recruiting

Other trials in France

About this study

Official title: Impact of Regorafenib in Combination With Multimodal Metronomic Chemotherapy on Progression-free Survival Compared With Standard Regorafenib for the Treatment of Chemo-resistant Metastatic Colorectal Cancers

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.

Being tested
Blood sample, Quality of life questionnaires, Biopsy, Regorafenib, Regorafenib + metronomic chemotherapy
Keywords
Regorafenib, metronomic chemotherapy, colon cancer
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood sampleProcedure or surgery

    Blood sample for plasma collection, Blood sample for ctDNA (circulating tumoral DNA) collection

  • Quality of life questionnairesOther

    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

  • BiopsyProcedure or surgery

    Fresh tumor biopsy at baseline and week 8

  • RegorafenibDrug

    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 chemotherapyCombination product

    • 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.
Study groups in NCT06425133
Study groupRoleWhat they receive
RegorafenibActive comparator• 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.
Receives: Procedure: Blood sample; Other: Quality of life questionnaires; Procedure: Biopsy; Drug: Regorafenib
Regorafenib+ metronomic chemotherapy + aspirinExperimental• 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.
Receives: Procedure: Blood sample; Other: Quality of life questionnaires; Procedure: Biopsy; Combination Product: Regorafenib + metronomic chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To evaluate the impact of a Regorafenib combined with metronomic chemotherapy and low-dose aspirin compared to standard Regorafenib treatment by assessing progression-free survival

    Progression-free survival (PFS): defined as the time from the randomization to objective disease progression as per RECIST v1.1 or death from any cause, whichever occurs first. The time of the progression or recurrence event is determined using the first date when there is documented evidence that the criteria have been met, even in situations where progression is observed after one or more missed visits, treatment discontinuation, or new anti-cancer treatment.

    Patients with no defined events observed during the follow up period will be censored at the date of last news

    Measured: 5 months average

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2024
  2. Study start19 Jul 2024
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
174 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06425133
Sponsor's protocol ID
2023/805
Acronym
CARE
Status last verified
Nov 2026
First submitted
17 May 2024
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Blood sample, Quality of life questionnaires and Biopsy in people with Metastatic Colorectal Cancer, run by Centre Hospitalier Universitaire de Besancon at 13 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Angélique VIENOT, Dr (+33 370632278, a3vienot@chu-besancon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To evaluate the impact of a Regorafenib combined with metronomic chemotherapy and low-dose aspirin compared to standard Regorafenib treatment by assessing progression-free survival (time frame: 5 months average). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06425133.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.

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