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

NCT06640166 | Recruiting Phase 2

• 2 other identifiers: 60702023-508615-24-00
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Colorectal Carcinoma; Colorectal Neoplasms; Colorectal Tumor; Colorectal Adenocarcinoma; Colorectal Cancer (CRC); Colorectal Cancer; Colon Cancer; Colon Adenocarcinoma; Colon Carcinoma; Colon Neoplasm

Keywords

BRAF; V600E; encorafenib; cetuximab; colorectal cancer; FOLFIRI; BRAF V600E

Outcome Measures

Primary Outcomes (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).

  6 months after the enrollment of the last patient.

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  6 months after the enrollment of the last patient.

• Overall Survival (OS)

  6 months after the enrollment of the last patient.

• Duration of response (DOR)

  6 months after the enrollment of the last patient.

• Overall Response Rate (ORR)

  6 months after the enrollment of the last patient.

• Disease Control Rate (DCR)

  6 months after the enrollment of the last patient.

Study Arms (1)

encorafenib+cetuximab+FOLFIRI

EXPERIMENTAL

Encorafenib plus cetuximab beyond progression in combination with irinotecan-based doublet chemoterapy (FOLFIRI)

Drug: encorafenib + cetuximab + FOLFIRI

Interventions

encorafenib + cetuximab + FOLFIRI DRUG

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).

Also known as: encorafenib, cetuximab, FOLFIRI

encorafenib+cetuximab+FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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;

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• Pierre Fabre Pharma GmbH: collaborator

Study Sites (3)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli, IRCCS

Roma, 00136, Italy

RECRUITING

Ospedale Cardinale G. Panico

Tricase, 73039, Italy

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Interventions

encorafenib; Cetuximab; IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maria Alessandra Calegari

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Alessandra Calegari

CONTACT

+39 06 30156318; mariaalessandra.calegari@policlinicogemelli.it

Maria Alessandra Calegari

CONTACT

+39 06 30156318; eclypsestudy@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 15, 2024
• Study Start: June 3, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 12, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)