AzTrials
AzTrials

Metastatic Colorectal CancerPhase 2/3REPROGRAM-02NCT05462613

Regorafenib With Low-dose Chemotherapies and Aspirin Followed by Standard Chemotherapies in Metastatic Colorectal Cancer

A Phase 2/3 study testing quality of life questionnaires, Blood sample and Regorafenib in people with Metastatic Colorectal Cancer, run by Centre Hospitalier Universitaire de Besancon at 14 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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 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?
quality of life questionnaires, Blood sample and Regorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
446 participants
Where
14 sitesFrance
Study dates
9 May 2023to Nov 2030
Phase
Phase 2/3
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 a first line of chemotherapy +/- targeted therapy
  • 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)
Show all 31Show fewer
  • 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.
  • 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.
  • Life expectancy of at least 3 months
  • Female or male with age ≥18 years old
  • Performance status Eastern Cooperative Oncology Group World Health Organization (ECOG-WHO) ≤1 (Appendix 1),
  • Measurable disease defined according to RECIST v1.1 (scanner or MRI)
  • 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.
  • 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
  • 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 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),
  • 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. Patients might be included at least 21 days following the last investigational agent administration.
  • 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,
  • 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,
  • Previous exposure to regorafenib,
Show all 34Show fewer
  • Previous exposure to other anti-angiogenic treatment than bevacizumab,
  • Complete deficit in dihydropyrimidine dehydrogenase (DPD),
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication,
  • Pregnant or breast-feeding subjects,
  • Congestive Heart Failure ≥ New York Heart Association (NYHA) class 2, unstable angina (anginal symptomatology at rest),
  • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),
  • Myocardial infarction less than 6 months before start of study drug,
  • Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted),
  • 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
  • Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea),
  • Ongoing infection >grade 2 CTCAE V5 (Appendix 6 ),
  • Known History of human immunodeficiency virus (HIV) infection,
  • Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy,
  • Subjects with seizure disorder requiring medication,
  • History of organ allograft,
  • Subjects with evidence or history of any bleeding diathesis, irrespective of severity,
  • Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication,
  • Serious, Non-healing wound, active ulcer or untreated bone fracture,
  • History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to inclusion,
  • Dehydration CTCAE v4 grade ≥1,
  • Known hypersensitivity to any of the study drugs, study drug classes or excipient in the formulation,
  • Interstitial lung disease with ongoing signs or symptoms,
  • Persistent proteinuria of CTCAE Grade 3 (>3.5 g/24 hours),
  • Subject unable to swallow oral medications,
  • 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,
  • Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks,
  • Treatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN,
  • Co-administration of drugs potentially interacting with regorafenib i.e. CYP3A4 or UGT1A9 (UDP-glucuronosyltransferase 1-9) inducers/inhibitors.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

France14 sites

  • CHU de Besançon

    Besançon

  • CHU Estain

    Clermont-Ferrand

  • Hôpital Henri Mondor

    Créteil

  • Centre Georges François Leclerc

    Dijon

  • Hôpital Privé Jean Mermoz

    Lyon

  • Hôpital Nord Franche Comté

    Montbéliard

  • CHU Montpellier

    Montpellier

  • Groupe hospitalier de la région de Mulhouse et Sud Alsace

    Mulhouse

  • Centre Antoine Lacassagne

    Nice

  • Hôpital Européen Georges Pompidou

    Paris

  • Hôpital la Pitié-Salpétrière

    Paris

  • Hôpital Saint antoine

    Paris

  • Institut Mutualiste Montsouris

    Paris

  • CHU de Reims - Hôpital Robert Debré

    Reims

Other trials in France

About this study

Official title: 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

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

Being tested
quality of life questionnaires, Blood sample, Regorafenib, Metronomic chemotherapies, Aspirin
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • quality of life questionnairesOther

    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 sampleProcedure or surgery

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

  • RegorafenibDrug

    • 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 chemotherapiesDrug

    • Capecitabine: 625mg/m²/orally twice daily continuously during the first two months
    • Cyclophosphamide: 50 mg per os, daily, for two months

  • AspirinDrug

    75 mg orally and daily during two months

  • BevacizumabDrug

    5 mg/Kg every 2 weeks according to investigator practice, until disease progression or unacceptable toxicity

  • FOLFIRI or FOLFOXDrug

    every 2 weeks according to investigator practice

Study groups in NCT05462613
Study groupRoleWhat they receive
ExperimentalExperimentalRegorafenib + metronomic Capecitabine + metronomic Cyclophosphamide + low-dose Aspirin followed by second line of chemotherapy (Bevacizumab + FOLFOX or FOLFIRI)
Receives: Other: quality of life questionnaires; Procedure: Blood sample; Drug: Regorafenib; Drug: Metronomic chemotherapies; Drug: Aspirin; Drug: Bevacizumab; Drug: FOLFIRI or FOLFOX
ControlActive comparatorSecond line of chemotherapy (Bevacizumab + FOLFOX or FOLFIRI)
Receives: Other: quality of life questionnaires; Procedure: Blood sample; Drug: Bevacizumab; Drug: FOLFIRI or FOLFOX

What is being measured

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

  1. best objective response during treatment period (phase II)

    the best response rate evaluated with RECIST v1.1 criteria per an independent radiologist committee during the treatment period defined as the number of with complete response (CR) or partial response (PR) as best response divided by the total number of patients evaluable. Patients for whom best overall tumor response is not CR or PR will be considered non-responders.

    Measured: during treatment period (from first treatment administration and disease progression, an average of 14 months

  2. overall survival (OS) (phase III)

    Overall survival is defined as the time from the randomization to death from any cause.

    Measured: through study completion, an average of 64 months

Timeline

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

  1. First posted18 Jul 2022
  2. Study start9 May 2023
  3. Primary completionNov 2029 (estimated)
  4. Study completionNov 2030 (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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
446 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05462613
Sponsor's protocol ID
2022/702
Acronym
REPROGRAM-02
Status last verified
Nov 2026
First submitted
8 Jul 2022
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing quality of life questionnaires, Blood sample and Regorafenib in people with Metastatic Colorectal Cancer, run by Centre Hospitalier Universitaire de Besancon at 14 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 31 inclusion and 34 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: under way, not looking for participants, 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 14 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

best objective response during treatment period (phase II) (time frame: during treatment period (from first treatment administration and disease progression, an average of 14 months). The study lists 2 primary outcomes in all. 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 NCT05462613.

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.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in