AzTrials
AzTrials

Colorectal CarcinomaPhase 2ECLYPseNCT06640166

Encorafenib + Cetuximab Beyond Progression in Combination With FOLFIRI in Patients With BRAF V600E Mutated Metastatic Colorectal Cancer Progressing on Encorafenib + Cetuximab.

A Phase 2 study testing encorafenib + cetuximab + FOLFIRI in people with Colorectal Carcinoma and Colorectal Neoplasms, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 3 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The aim of this study is to determine the activity of encorafenib plus cetuximab in combination with FOLFIRI in patients with BRAF V600E mutated metastatic colorectal cancer progressing on encorafenib plus cetuximab administered in second line. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
encorafenib + cetuximab + FOLFIRI
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
3 sitesItaly
Study dates
3 Jun 2024to 30 Jun 2026
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

  • written informed consent to study procedures;
  • age ≥ 18 years;
  • histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma;
  • radiological evidence of metastatic disease;
  • evidence of measurable disease according to RECIST 1.1 criteria;
  • presence of BRAF V600E mutation in tumor tissue (primary CRC and/or related metastasis) as previously determined by a local assay at any time prior to screening (only PCR and NGS-based local assays results will be acceptable);
Show all 29Show fewer
  • disease progression while on treatment with EC received in 2nd line setting
  • EC administered after disease relapse during treatment or within 6 months following adjuvant therapy will be second line;
  • maintenance therapy given in the metastatic setting after a first line doublet or triplet chemotherapy will not be considered a separate regimen;
  • best response to previous treatment with EC: CR, PR or SD lasting for at least 3 months.
  • patient fit for a subsequent treatment line with FOLFIRI. Patients exposed to irinotecan and fluoropyrimidines during previous line for metastatic disease are eligible, provided that the patient has recovered from G3 toxicity;
  • life expectancy ≥ 3 months;
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1.
  • Adequate bone marrow function at screening:
  • Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
  • Platelets ≥ 100 × 10^9/L;
  • Hemoglobin ≥ 9.0 g/dL;
  • Note: Transfusions will be allowed to achieve this. Transfusions will be permitted provided that the patient has not received more than 2 units red blood cells in the prior 4 weeks to achieve this criteria.
  • Adequate renal function at screening: serum creatinine ≤ 1.5 × upper limit of normal (ULN), or calculated by Cockroft-Gault formula, or directly measured creatinine clearance ≥ 50 mL/min at screening.
  • Adequate hepatic function at screening:
  • serum total bilirubin ≤ 1.5 × ULN;
  • alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in presence of liver metastases.
  • Adequate cardiac function characterized by the following at screening: QT interval corrected for heart rate using Fridericia's formula (QTcF) value ≤480 msec.
  • Availability of treatment-naïve, archival FFPE tumor tissue sample.
  • Ability to take oral medications.
  • Male subjects with female partners of childbearing potential must be willing to use adequate contraception, starting with the first dose of study therapy through 180 days after the last dose of treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Women of childbearing potential must have a negative blood or urine pregnancy test at the baseline visit.
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study starting with the first dose of study therapy through 180 days after the last dose of treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Will and ability to comply with the protocol.

Who cannot join

  • patients experiencing PD as best response to EC;
  • patients with specific BRAFi/AntiEGFR contraindications;
  • patients with specific irinotecan or fluoropyrimidines contraindications;
  • patients with DPYD deficiency;
  • life expectancy ≤3 months;
  • ECOG PS >1.
Show all 22Show fewer
  • Any of the following in the 6 months prior to treatment start: myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft [CABG], coronary angioplasty or stenting), congestive heart failure (≥ New York Heart Association Classification Class II), serious cardiac arrhythmia (except atrial fibrillation and appropriately controlled paroxysmal supraventricular tachycardia), cerebrovascular accident, symptomatic pulmonary embolism.
  • Congenital long QT syndrome.
  • Impaired gastrointestinal function or disease that may significantly alter the absorption of encorafenib (uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).
  • Uncontrolled coagulopathy.
  • Patients has a known history of Gilbert's syndrome or is known to have any of the following genotypes: UGT1A1*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28.
  • Active infection requiring systemic therapy.
  • Known history of acute or chronic pancreatitis.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
  • Symptomatic brain metastasis or leptomeningeal disease. Prior hypersensitivity or toxicity that would suggest an inability to tolerate administration of the planned dose of investigational products.
  • Residual CTCAE > Grade 2 toxicity from any prior anticancer therapy, with the exception of alopecia or neuropathy.
  • Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies, including current treatment with a non-topical medication known to be a strong inhibitor of cytochrome P450 (CYP) 3A4 ≤ 1 week prior to the start of study treatment.
  • Concomitant use of St. John's Wort (hypericum perforatum).
  • Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study.
  • Concurrent or previous other malignancy within the past 3 years, with the exception of effectively treated squamous cell or basal cell skin cancer, melanoma in situ, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, carcinoma in situ of the colon or rectum, or other noninvasive or indolent malignancy without Sponsor approval.
  • Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study and until 180 days after the last trial treatment.

Trial locations and contacts

3 sites in 1 country.

Maria Alessandra Calegari contact

+39 06 30156318

mariaalessandra.calegari@policlinicogemelli.it

Maria Alessandra Calegari contact

+39 06 30156318

eclypsestudy@policlinicogemelli.it

Italy3 sites, 3 recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

    Federica Morano, +39 02 23901, federica.morano@istitutotumori.mi.it

    Not yet recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli, IRCCS

    Roma, 00136

    Maria Alessandra Calegari, +39 06 30156318, mariaalessandra.calegari@policlinicogemelli.it

    Recruiting

  • Ospedale Cardinale G. Panico

    Tricase, 73039

    Emiliano Tamburini, +39 0833 773111, oncologia.trials@piafondazionepanico.it

    Recruiting

Other trials in Italy

About this study

The aim of this study is to determine the activity of encorafenib plus cetuximab in combination with FOLFIRI in patients with BRAF V600E mutated metastatic colorectal cancer progressing on encorafenib plus cetuximab administered in second line.

Read the detailed description

This is a prospective, multicentre, phase II single-arm trial, evaluating encorafenib plus cetuximab beyond progression in combination with irinotecan-based doublet chemotherapy (FOLFIRI) in patients affected by BRAF V600E mutated metatstic colorectal cancer progressing on encorafenib plus cetuximab administered in second line.

Eligible patients are:

  • affected by BRAF V600E mutated metastatic colorectal cancer;
  • progressing on encorafenib plus cetuximab administered in second line;
  • achieved complete response, or partial response, or stable disease lasting more than 3 moths, as best response to encorafenib plus cetuximab administered in second line.

All patients eligible according to inclusion and exclusion criteria will receive encorafenib plus cetuximab beyond progression in combination with irinotecan-based doublet chemoterapy (FOLFIRI) as follows:

  • encorafenib 300 mg (75 mgx4 hard capsules) orally once daily;
  • cetuximab 500 mg/sqm iv every 14 days;
  • FOLFIRI iv every 14 days (Irinotecan 180 mg/sqm, Folinic Acid 400 mg/sqm, 5Fluorouracil 400 mg/sqm iv bolus and 2400 mg/sqm iv continuous infusion over 46-48 hours).

Treatment will be administered until disease progression, unacceptable toxic effects, withdrawal of consent, or death.

The primary end point of this trial is investigator-assessed 6-month progression free survival rate and is defined as the proportion of patients alive and progression-free by the 6-month time point from start of investigational treatment (encorafenib plus cetuximab beyond progression in combination with FOLFIRI).

Being tested
encorafenib + cetuximab + FOLFIRI
Keywords
BRAF, V600E, encorafenib, cetuximab, colorectal cancer, FOLFIRI, BRAF V600E
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.

  • encorafenib + cetuximab + FOLFIRIDrug

    Also called encorafenib, cetuximab, FOLFIRI

    encorafenib plus cetuximab beyond progression in combination with irinotecan-based doublet chemoterapy (FOLFIRI) as follows:

    • encorafenib 300 mg (75 mgx4 hard capsules) orally once daily;
    • cetuximab 500 mg/sqm iv every 14 days;
    • FOLFIRI iv every 14 days (Irinotecan 180 mg/sqm, Folinic Acid 400 mg/sqm, 5Fluorouracil 400 mg/sqm iv bolus and 2400 mg/sqm iv continuous infusion over 46-48 hours).
Study groups in NCT06640166
Study groupRoleWhat they receive
encorafenib+cetuximab+FOLFIRIExperimentalEncorafenib plus cetuximab beyond progression in combination with irinotecan-based doublet chemoterapy (FOLFIRI)
Receives: Drug: encorafenib + cetuximab + FOLFIRI

What is being measured

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

  1. 6-month Progression Free Survival rate

    The proportion of patients alive and progression-free by the 6-month time point from start of investigational treatment (encorafenib plus cetuximab beyond progression in combination with FOLFIRI). Progression free survival is defined as the time elapsed between start of investigational treatment and the date of first event (progression or death, whichever occurs first).

    Measured: 6 months after the enrollment of the last patient.

Secondary outcomes (6)

  1. Progression Free Survival (PFS)

    Time elapsed from start of investigational treatment to the documentation of investigator-assessed disease progression, according to RECIST 1.1, or death due to any cause, whichever occurs first.

    Measured: 6 months after the enrollment of the last patient.

  2. Overall Survival (OS)

    Time elapsed from start of investigational treatment to the date of death due to any cause.

    Measured: 6 months after the enrollment of the last patient.

  3. Duration of response (DOR)

    Time from response, in patients who achieve partial response (PR) or complete response (CR), to disease progression or death.

    Measured: 6 months after the enrollment of the last patient.

  4. Overall Response Rate (ORR)

    Percentage of patients who achieve PR or CR as measured by RECIST 1.1 criteria.

    Measured: 6 months after the enrollment of the last patient.

  5. Disease Control Rate (DCR)

    percentage of patients who achieve PR, CR or stable disease (SD) as measured by RECIST 1.1 criteria.

    Measured: 6 months after the enrollment of the last patient.

  6. Rate of adverse events

    Number of participants with treatment-related adverse events (graded according to NCI CTCAE version 4.03)

    Measured: 6 months after the enrollment of the last patient.

Timeline

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

  1. First posted15 Oct 2024
  2. Study start3 Jun 2024
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion30 Jun 2026 (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
NCT06640166
Sponsor's protocol ID
6070
Other IDs
2023-508615-24-00, 2023
Acronym
ECLYPse
Status last verified
Oct 2024
First submitted
7 Oct 2024
Last updated
12 Feb 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 encorafenib + cetuximab + FOLFIRI in people with Colorectal Carcinoma and Colorectal Neoplasms, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 3 sites in Italy.

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 29 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 12 Feb 2025. 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 Italy. 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?

Results are not available in the source record.

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

Contact Maria Alessandra Calegari (+39 06 30156318, mariaalessandra.calegari@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-month Progression Free Survival rate (time frame: 6 months after the enrollment of the last patient.). 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 NCT06640166.

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 12 Feb 2025.

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