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Colo-rectal CancerPhase 2REPROGRAM-01NCT04534218

Regorafenib in Combination With Metronomic Chemotherapies, and Low-dose Aspirin in Metastatic Colorectal Cancer

A Phase 2 study testing Regorafenib, Cyclophosphamide and Capecitabine in people with Colo-rectal Cancer and Metastatic Cancer, run by Centre Hospitalier Universitaire de Besancon at 3 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The investigators propose a phase II clinical trial with the objective to investigate the potential clinical interest to associate regorafenib with a metronomic chemotherapy combining capecitabine, cyclophosphamide and low-dose aspirin, for the treatment of patients with metastatic colorectal cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colo-rectal Cancer, Metastatic Cancer
What is being tested?
Regorafenib, Cyclophosphamide and Capecitabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
3 sitesFrance
Study dates
16 Oct 2020to 13 Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

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, oxaliplatin, anti-VEGF and anti-EGFR therapy if KRAS and NRAS WT), 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 (scanner or MRI) (Annex 2)
  • 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
  • Imaging target greater than one cm must be visible on CT,
  • 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 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 (curatorship, tutorship) 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,
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  • Previous exposure to other anti-angiogenic treatment than bevacizumab and aflibercept,
  • Complete deficit in dihydropyrimidine deshydrogenase (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,
  • 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 v5 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 (V5) 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, CYP2C9 or UGT1A9 inducers/inhibitors.

Trial locations and contacts

3 sites in 1 country.

France3 sites

  • CHU de Besançon

    Besançon, 25030

  • Centre georges-François Leclerc

    Dijon, 21000

  • Hôpital Nord Franche-Comté

    Montbéliard

Other trials in France

About this study

Official title: Regorafenib in Combination With Metronomic Cyclophosphamide, Capecitabine, and Low-dose Aspirin in Metastatic Colorectal Cancer Carcinoma An Open-label Phase II

The investigators propose a phase II clinical trial with the objective to investigate the potential clinical interest to associate regorafenib with a metronomic chemotherapy combining capecitabine, cyclophosphamide and low-dose aspirin, for the treatment of patients with metastatic colorectal cancer. The main objective of the study will be to achieve 15% of objective response rate in patients treated with multimodal metronomic chemotherapy and regorafenib.

Keywords
regorafenib, metronomic chemotherapy, colon cancer
Medical subject headings
Colonic Neoplasms, Neoplasm Metastasis

What participants receive

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

  • RegorafenibDrug

    Also called Stivarga

    • 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 following cycles: regorafenib will be administered at a 80, 120 or 160 mg daily dose according to toxicity observed with the last dose used in the first cycle.

  • CyclophosphamideDrug

    Also called Endoxan

    50 mg per os, daily, for 6 months

  • CapecitabineDrug

    Also called Xeloda

    625mg/m²/orally twice daily continuously for 6 months

  • AspirinDrug

    Also called Kardegic

    75 mg orally and daily until progression

Study groups in NCT04534218
Study groupRoleWhat they receive
ExperimentalExperimentalREGORAFENIB: * 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 following cycles: regorafenib will be administered at a 80, 120 or 160 mg daily dose according to toxicity observed with the last dose used in the first cycle. METRONOMIC CHEMOTHERAPIES: * Capecitabine: 625mg/m²/orally twice daily continuously for 6 months * Cyclophosphamide: 50 mg per os, daily, for 6 months ASPIRIN: 75 mg orally and daily until progression
Receives: Drug: Regorafenib; Drug: Cyclophosphamide; Drug: Capecitabine; Drug: Aspirin

What is being measured

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

  1. objective response rate

    The objective response rate (ORR) will be defined by RECIST v1.1 criteria as the best disease response observed during the treatment period (assessed to 4 months). ORR rate is defined as the proportion of patients whose tumor regresses or does not progress under treatment.

    Measured: From date of inclusion until end of treatment for the patient, assessed to 4 months

Timeline

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

  1. First posted1 Sep 2020
  2. Study start16 Oct 2020
  3. Primary completion13 Dec 2023
  4. Study completion13 Dec 2023

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04534218
Sponsor's protocol ID
2020/490
Acronym
REPROGRAM-01
Status last verified
Nov 2024
First submitted
16 Jul 2020
Last updated
20 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • El Kaddissi A, Vienot A, Fumet JD, Meurisse A, Nguyen T, Klajer E, Bouard A, Spehner L, Fein F, Stouvenot M, Dochy E, Rebucci-Peixoto M, Almotlak H, Henriquez J, Selmani Z, Vernerey D, Hervouet E, Folletet A, Kim S, Ghiringhelli F, Borg C. Regorafenib and metronomic capecitabine, cyclophosphamide, and aspirin in refractory metastatic colorectal cancer: results from the REPROGRAM-01 single-arm phase II trial. ESMO Gastrointest Oncol. 2025 Dec 3;10:100270. doi: 10.1016/j.esmogo.2025.100270. eCollection 2025 Dec.

    PubMed 42404549

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib, Cyclophosphamide and Capecitabine in people with Colo-rectal Cancer and Metastatic Cancer, run by Centre Hospitalier Universitaire de Besancon at 3 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 16 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: finished, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

objective response rate (time frame: From date of inclusion until end of treatment for the patient, assessed to 4 months). 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 NCT04534218, which also lists 1 linked publication.

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 20 Dec 2024.

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