Trial Title:
Cetuximab and Envafolimab Plus mFOLFOXIRI as First-line Treatment for RAS/BRAF Wild-type, MSS, Unresectable Left-side Metastatic Colorectal Cancer
NCT ID:
NCT05959356
Condition:
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Leucovorin
Oxaliplatin
Irinotecan
Cetuximab
Levoleucovorin
Conditions: Keywords:
First-line treatment
RAS/BRAF wild-type
Microsatellite stable(MSS)
Unresectable left-side metastatic colorectal cancer
Envafolimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cetuximab + Envafolimab + mFOLFOXIRI
Description:
Cetuximab 500mg/m² + envafolimab 200mg + irinotecan 150 mg/m² + oxaliplatin 85 mg/m² +
leucovorin 200 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle up to
max 8 cycles, followed by maintenance with cetuximab 500mg/m² + envafolimab 200mg +
leucovorin 200 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle until
PD, unacceptable toxicity or patient's refusal.
Arm group label:
Arm A
Other name:
Cetuximab or c225
Other name:
Envafolimab
Other name:
Irinotecan
Other name:
Oxaliplatin
Other name:
Leucovorin
Other name:
5-FU
Intervention type:
Drug
Intervention name:
Cetuximab + mFOLFOX6/FOLFIRI
Description:
Cetuximab 500mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2400 mg/m² civ.
46h or cetuximab 500mg/m² + irinotecan 180 mg/m² + leucovorin 200 mg/m² + 5-FU 2400 mg/m²
civ. 46h all on day 1 of each 2 weeks cycle up to max 8 cycles, followed by maintenance
with cetuximab 500mg/m² + leucovorin 200 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of
each 2 weeks cycle until PD, unacceptable toxicity or patient's refusal.
Arm group label:
Arm B
Other name:
Cetuximab or c225
Other name:
Irinotecan
Other name:
Oxaliplatin
Other name:
Leucovorin
Other name:
5-FU
Summary:
The primary aim of phase II CEIL study is to evaluate the efficacy of cetuximab and
envafolimab plus mFOLFOXIRI versus cetuximab plus mFOLFOX6/FOLFIRI as first line
treatment of patients with initially unresectable and previously untreated RAS/BRAF
wild-type, MSS, left-side metastatic colorectal cancer(mCRC), in terms of
Progression-free Survival.
Detailed description:
This is a prospective, open-label, multicentric, randomized controlled phase II trial in
which patients with initially unresectable and previously untreated RAS/BRAF wild-type,
MSS, left-side mCRC will be randomized to two therapy groups:
Experimental arm A: receive induction treatment with cetuximab and envafolimab plus
mFOLFOXIRI up to 8 cycles followed by maintenance with cetuximab and envafolimab plus
5-FU/LV until disease progression, unacceptable toxicity or patient's refusal.
Standard arm B: receive induction treatment with cetuximab plus mFOLFOX6/FOLFIRI up to 8
cycles followed by maintenance with cetuximab plus 5-FU/LV until disease progression,
unacceptable toxicity or patient's refusal.
The second- and subsequent lines of treatment will be at investigators' choice.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Signed informed consent obtained before any study specific procedures. Subjects must
be able to understand and willing to sign a written informed consent.
- Male or female subjects ≥ 18 years, expected lifespan ≥ 12 weeks.
- Patients have histologically or cytologically confirmed RAS and BRAF wild-type, MSS
metastatic colorectal adenocarcinoma (mCRC), excluding appendiceal and anal cancers.
- AJCC/UICC stage IV left-side metastatic colorectal cancer. At least one measurable
lesion according to RECIST 1.1.
- The patient has not previously received any systemic treatment specifically
targeting advanced or metastatic colorectal cancer, including chemotherapy,
monoclonal antibodies such as cetuximab or panitumumab targeting the epidermal
growth factor receptor (EGFR), bevacizumab targeting the vascular endothelial growth
factor (VEGF), immune checkpoint inhibitors such as anti-PD-1 or anti-PD-L1
antibodies, and anti-CTLA-4 antibodies. If recurrence or metastasis occurs during or
within 6 months after adjuvant or neoadjuvant chemotherapy, adjuvant/neoadjuvant
therapy is considered as a first-line systemic treatment for advanced or metastatic
disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Within 7 days before treatment, the following laboratory test values are obtained
and appropriate organ function is present:
Hemoglobin ≥ 90g/L, neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 75 × 10^9/L; Serum
total bilirubin ≤ 1.5 × upper limit of normal (UNL); Aspartate aminotransferase (AST) or
alanine aminotransferase (ALT) ≤ 2.5 × UNL; if there are liver metastases, AST or ALT ≤ 5
× UNL; Serum creatinine ≤ 1.5 × UNL.
- Women of childbearing potential must have a negative blood pregnancy test at the
baseline visit. For this trial, women of childbearing potential are defined as all
women after puberty, unless they are postmenopausal for at least 12 continuous
months, are surgically sterile, or are sexually inactive.
- Patients are not allowed to participate in other clinical trials during the study
period and willing to comply with the study protocol and visit plan.
Exclusion Criteria:
- Concurrent active malignancy, excluding malignancies with disease-free survival of 5
years or more or in situ carcinoma considered cured after adequate treatment.
- Currently diagnosed with gastrointestinal diseases such as duodenal ulcer,
ulcerative colitis, intestinal obstruction, or other conditions determined by the
investigator to potentially cause gastrointestinal bleeding or perforation.
- Experienced thrombotic or embolic events, such as cerebrovascular accidents
(including transient ischemic attacks), pulmonary embolism, or deep vein thrombosis,
within the 12 months prior to study enrollment.
- Experienced the following conditions within the 12 months prior to study enrollment:
myocardial infarction, severe/unstable angina pectoris, New York Heart Association
(NYHA) class II or above heart failure, clinically significant supraventricular or
ventricular arrhythmias, or symptomatic congestive heart failure.
- Use of systemic antibiotics for ≥7 days within the 4 weeks prior to study
enrollment, or the occurrence of unexplained fever (>38.5°C) during the screening
period/prior to the first dose (fever attributed to the tumor can be considered for
enrollment, as determined by the investigator).
- Presence of uncontrolled pleural effusion, ascites, or pericardial effusion within
14 days prior to study enrollment despite appropriate treatment.
- Presence of any unresolved adverse events of Grade 2 or higher (excluding anemia,
alopecia, and skin pigmentation) attributed to previous treatments according to the
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
version 5.0.
- Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled
systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute
pneumonia).
- Known human immunodeficiency virus (HIV) infection or known active hepatitis
(defined as HBV-DNA ≥ 500 IU/ml for hepatitis B, and HCV-RNA above the limit of
detection for hepatitis C) or co-infection with hepatitis B and C.
- History of known or suspected allergy to any investigational drug used in the study.
- Pregnancy or lactation in women.
- Pre-menopausal women (last menstrual period <2 years ago) who do not use or refuse
to use effective non-hormonal contraception, or fertile men.
- Presence of other significant physical or mental illnesses or laboratory
abnormalities that may increase the risk of participation in the study, interfere
with study results, or are deemed unsuitable for participation by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The First People's Hospital of Foshan
Address:
City:
Foshan
Zip:
528000
Country:
China
Status:
Recruiting
Contact:
Last name:
Wei Wang, Ph.D
Phone:
8618666392971
Facility:
Name:
The Sixth Affiliated Hospital of Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510655
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanhong Deng, Ph.D
Phone:
8613925106525
Email:
dengyanh@mail.sysu.edu.cn
Facility:
Name:
Affiliated Cancer Hospital of Guizhou Medical University
Address:
City:
Guiyang
Zip:
550000
Country:
China
Status:
Recruiting
Contact:
Last name:
Wen-Ling Wang, Ph.D
Phone:
8613885077539
Start date:
November 9, 2023
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Sun Yat-sen University
Agency class:
Other
Source:
Sun Yat-sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05959356
