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Colo-rectal CancerPhase 2REFISHNCT07178717

A Study to Characterize Encorafenib Plus Cetuximab as Rechallenge Treatment for BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy With BRAF Inhibitors-based Combinations

A Phase 2 study testing Rechalange with bevacizumab + encorafenib in people with Colo-rectal Cancer, run by Vall d'Hebron Institute of Oncology at 1 site in Spain.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is an open-label, unicentre, single-arm Phase 2 study of encorafenib and cetuximab as rechallenge treatment in patients with BRAF V600E-mutant metastatic colorectal cancer after previous therapy with BRAF inhibitors-based combinations. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colo-rectal Cancer
What is being tested?
Rechalange with bevacizumab + encorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteSpain
Study dates
Oct 2025to Aug 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

  • Provision of signed and dated informed consent form.
  • Age ≥18 years at the time of informed consent.
  • Histologically- or cytologically confirmed mCRC that is metastatic.
  • Presence of confirmed BRAF V600E mutation.
  • Eligible to receive cetuximab and encorafenib per locally approved label with regard to tumor RAS status.
  • Patients must be previously treated with at least 2 prior regimens for metastatic disease and had demonstrated progressive disease or intolerance to their last regimen. Prior standard chemotherapy must include the following agents: fluoropyrimidine in monotherapy or in combination with irinotecan and/or oxaliplatin with or without anti-VEGF. Combination of chemotherapy with BRAF inhibitor-containing regimen is also permitted.
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  • Patients must have received BRAF inhibitor plus anti-EGFR combinations (including but not limited to MEK or ERK inhibitors or chemotherapy) treatment for ≥ 4 months. Patients must have had complete response, partial response or stable disease >6 months during the BRAF inhibitor-based treatment.
  • Patients at study enrollment should have at least 4 months interval since the last administration of BRAF inhibitors.
  • Life expectancy >12 weeks, as determined by the investigator.
  • Patients must have progressed during or within 6 months of the last chemotherapy regimen > Patients who received adjuvant/neoadjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant/neoadjuvant chemotherapy are permitted to count the adjuvant/neoadjuvant therapy as one regimen for advanced disease.
  • Measurable disease according to RECIST v1.1.
  • ECOG performance status 0-1.
  • Adequate bone marrow function characterized by the following at screening:
  • Absolute neutrophil count (ANC) ≥1.5 x 10^9/L.
  • Platelets ≥100 x 10^9/L.
  • Hemoglobin ≥9.0 g/dL (with or without blood transfusions).
  • Adequate hepatic and renal function characterized by the following at screening:
  • Serum total bilirubin ≤1.5 x upper limit of normal (ULN) and <2 mg/dL. Note: Total bilirubin >1.5 x ULN is allowed if direct (conjugated) ≤1.5 x ULN and indirect (unconjugated) bilirubin is ≤4.25 x ULN.
  • Note: Participants with hyperbilirubinemia due to non-hepatic cause (e.g., hemolysis, hematoma) may be enrolled following discussion and agreement with the Sponsor medical monitor.
  • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤2.5 x ULN, or ≤5 x ULN in the presence of liver metastases.
  • Adequate renal function defined by an estimated creatinine clearance ≥50 mL/min according to the Cockcroft Gault formula or by 24-hour urine collection for creatinine clearance, or according to local institutional standard method.
  • Protein < 2+ on dipstick urinalysis or ≤ 1.0 g in a 24-hour urine collection. All patients with ≥2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein.
  • Adequate electrolytes, defined as serum potassium and magnesium levels within institutional normal limits.
  • Note: Replacement treatment to achieve adequate electrolytes will be allowed.
  • Adequate cardiac function characterized by the following at screening:
  • Mean triplicate QT interval corrected for heart rate using Fridericia's formula (QTcF) value ≤480 msec.
  • Able to take oral medications.
  • Highly effective contraception for both male and female subjects if the risk of conception exists during and at least up to 2 months after the last study medication.

Who cannot join

  • Treatment with another investigational drug or participation in another investigational study at enrolment or within 30 days prior to enrollment.
  • Patient unable to comply with the study protocol owing to psychological, social (lack of social support or social exclusion) or geographical reasons.
  • Patient is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
  • Known history of chronic pancreatitis.
  • Tumors with microsatellite instability or mismatch repair deficiency if they have not received a PD1/PDL1 inhibitor-based treatment, unless medical contraindication.
  • History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months before the enrollment in the study.
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  • Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
  • History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft [CABG], coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment.
  • Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality ≤ 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia.
  • Impaired hepatic function, defined as Child-Pugh class B or C.
  • Known history of human immunodeficiency virus (HIV), active hepatitis B virus (HBV) infection or active hepatitis C virus (HCV) infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients with past exposure to HBV are also eligible for the study provided they are negative for HBV DNA.
  • Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study.
  • Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and the enrollment in the study.
  • Subjects with leptomeningeal carcinomatosis.
  • Impaired gastrointestinal (GI) function or disease that may significantly alter the absorption of encorafenib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).
  • Knowledge of any other disease or medication that may interfere with study treatment.
  • Presence of any contraindication with regard to the study drugs as specified in the corresponding SmPCs.
  • Patients who achieved progression disease as best response while receiving BRAF inhibitor previously.

Trial locations and contacts

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

Spain1 site

  • Hospital Universitari Vall d'Hebron

    Barcelona, Barcelona, 08035

    Francisco Javier Ros Montaña, fjros@vhio.net

Other trials in Spain

About this study

Official title: A Phase 2, Single-Arm Study of Encorafenib Plus Cetuximab as Rechallenge Treatment of BRAF V600E-mutant Metastatic Colorectal Cancer Patients After Previous Therapy With BRAF Inhibitors-based Combinations: the RefIsh Trial

This is an open-label, unicentre, single-arm Phase 2 study of encorafenib and cetuximab as rechallenge treatment in patients with BRAF V600E-mutant metastatic colorectal cancer after previous therapy with BRAF inhibitors-based combinations.

The study aims to evaluate the antitumor activity of encorafenib plus cetuximab as a rechallenge strategy measured by progression-free survival rate at 4 months.

Eligible patients (a total of 25) will receive encorafenib 300 mg (four 75 mg capsules) once daily (q.d) in 28-day cycles plus intravenous cetuximab at 500 mg/m2 every 2 weeks (Q2W). Treatment will be administered until progression, unacceptable toxicity, patient request, physician's decision or subsequent anticancer therapy.

Being tested
Rechalange with bevacizumab + encorafenib
Medical subject headings
Colonic Neoplasms

What participants receive

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

  • Rechalange with bevacizumab + encorafenibDrug

    Patients will receive encorafenib 300mg once daily plus cetuximab 500mg/m2 every 2 weeks until disease progression, unacceptable toxicity, patient request, physician's decision to withdraw treatment, subsequent anticancer therapy or death.

Study groups in NCT07178717
Study groupRoleWhat they receive
Bevacizumab + encorafenibExperimentalNot described
Receives: Drug: Rechalange with bevacizumab + encorafenib

What is being measured

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

  1. Progression free survival

    Progression-free survival rate at 4 months (4-month PFS rate) according to RECIST V1.1 by Investigator assessment.

    Measured: 4 months since the start of treatment

Secondary outcomes (5)

  1. Progression-free survival

    Progression-free survival (PFS) according to RECIST V1.1 by Investigator assessment.

    Measured: From randomization until the first documented progression, assessed up to 30 months (expected)

  2. Objective response rate

    Description: Objective Response Rate (ORR) according to RECIST V1.1 by Investigator assessment.

    Measured: For the duration of the study, expected 30 months

  3. Overal Survival

    Overall survival (OS)

    Measured: From date of enrollment until death, up to the duration of the study (expected 30 months)

  4. Evaluate the safety and tolerability profile

    Incidence and severity of adverse events (AEs), graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Change in clinical laboratory test parameters, vital signs, ECGs and echocardiogram/MUGA scans.

    Measured: Through study completion, an average of 1 year

  5. Clinical efficacy

    Clinical efficacy based on the presence or absence of acquired genomic mechanism of resistance detected in the NGS baseline to the rechallenge.

    Measured: Through study completion, an average of 1 year"

Timeline

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

  1. First posted17 Sep 2025
  2. Study startOct 2025 (estimated)
  3. Primary completionFeb 2028 (estimated)
  4. Study completionAug 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07178717
Sponsor's protocol ID
VHIO23004
Other IDs
2023-509564-22-00, 2023
Acronym
REFISH
Status last verified
Sep 2025
First submitted
2 Sep 2025
Last updated
17 Sep 2025
Results posted
No
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 study testing Rechalange with bevacizumab + encorafenib in people with Colo-rectal Cancer, run by Vall d'Hebron Institute of Oncology at 1 site in Spain.

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 28 inclusion and 18 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: opening soon, as of the sponsor's last update on 17 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. 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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (time frame: 4 months since the start of treatment). 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 NCT07178717.

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 17 Sep 2025.

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