Trial Title:
Encorafenib + Cetuximab Beyond Progression in Combination With FOLFIRI in Patients With BRAF V600E Mutated Metastatic Colorectal Cancer Progressing on Encorafenib + Cetuximab.
NCT ID:
NCT06640166
Condition:
Colorectal Carcinoma
Colorectal Neoplasms
Colorectal Tumor
Colorectal Adenocarcinoma
Colorectal Cancer (CRC)
Colorectal Cancer
Colon Cancer
Colon Adenocarcinoma
Colon Carcinoma
Colon Neoplasm
Conditions: Official terms:
Carcinoma
Neoplasms
Colorectal Neoplasms
Adenocarcinoma
Colonic Neoplasms
Cetuximab
Conditions: Keywords:
BRAF
V600E
encorafenib
cetuximab
colorectal cancer
FOLFIRI
BRAF V600E
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
encorafenib + cetuximab + FOLFIRI
Description:
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).
Arm group label:
encorafenib+cetuximab+FOLFIRI
Other name:
encorafenib
Other name:
cetuximab
Other name:
FOLFIRI
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.
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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;
- 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.
Exclusion Criteria:
- 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).
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fondazione IRCCS Istituto Nazionale dei Tumori
Address:
City:
Milano
Zip:
20133
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Federica Morano
Phone:
+39 02 23901
Email:
federica.morano@istitutotumori.mi.it
Facility:
Name:
Fondazione Policlinico Universitario Agostino Gemelli, IRCCS
Address:
City:
Roma
Zip:
00136
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Maria Alessandra Calegari
Phone:
+39 06 30156318
Email:
mariaalessandra.calegari@policlinicogemelli.it
Facility:
Name:
Ospedale Cardinale G. Panico
Address:
City:
Tricase
Zip:
73039
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Emiliano Tamburini
Phone:
+39 0833 773111
Email:
oncologia@piafondazionepanico.it
Start date:
June 3, 2024
Completion date:
June 30, 2026
Lead sponsor:
Agency:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Agency class:
Other
Collaborator:
Agency:
Pierre Fabre Pharma GmbH
Agency class:
Industry
Source:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06640166
