Trial Title:
Neoadjuvant Serplulimab & Bevacizumab With FOLFOX vs. FOLFOX Alone in RAS/BRAF WT, pMMR/MSS CRC Patients
NCT ID:
NCT06280495
Condition:
Colorectal Cancer
Liver Metastases
Conditions: Official terms:
Colorectal Neoplasms
Neoplasm Metastasis
Bevacizumab
Oxaliplatin
Fluorouracil
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
This is a prospective, randomized, multicenter clinical trial. Stratified randomization
based on liver metastasis characteristics, including timing, number, and size, will be
conducted in eligible patients.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
5 mg/m2 IV on day 1
Arm group label:
FOLFOX only group
Arm group label:
Serplulimab + Bevacizumab + FOLFOX
Other name:
Eloxatin
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
400 mg/m2 IV bolus on day 1, followed by 2.4 g/m2 continuous IV infusion over 48 hours
Arm group label:
FOLFOX only group
Arm group label:
Serplulimab + Bevacizumab + FOLFOX
Other name:
5-FU
Intervention type:
Drug
Intervention name:
Serplulimab
Description:
200 mg IV infusion on day 1
Arm group label:
Serplulimab + Bevacizumab + FOLFOX
Other name:
anti-PD-1 antibody
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
5 mg/kg IV infusion on day 1
Arm group label:
Serplulimab + Bevacizumab + FOLFOX
Other name:
Avastin
Summary:
The primary objective of this study is to assess whether the addition of Serplulimab (a
PD-1 inhibitor) and Bevacizumab (an anti-angiogenesis agent) to the standard FOLFOX
chemotherapy can enhance the immune microenvironment in the liver, increase T lymphocyte
infiltration, and consequently improve the postoperative prognosis for patients with
surgically resectable colorectal cancer liver metastases (RAS/BRAF wild-type, pMMR/MSS)
compared to FOLFOX alone.
Detailed description:
In this prospective, multi-center clinical trial titled "INTENSIFY," we seek to evaluate
the potential benefits of integrating Serplulimab and Bevacizumab with the standard
FOLFOX chemotherapy regimen as neoadjuvant treatment for surgically resectable colorectal
cancer liver metastases (CRLM). Colorectal cancer remains a leading cause of global
cancer-related morbidity and mortality, with liver metastases accounting for a
significant proportion. Our primary objective is to investigate whether the addition of
Serplulimab, a PD-1 inhibitor, and Bevacizumab, an anti-angiogenesis agent, can improve
the postoperative prognosis for patients with RAS/BRAF wild-type, pMMR/MSS CRLM. We aim
to address critical questions regarding the efficacy of this combined treatment in
enhancing the immune microenvironment within the liver, ultimately leading to increased T
lymphocyte infiltration and improved patient outcomes. The study will involve a
randomized assignment of patients to either the standard FOLFOX chemotherapy arm or the
experimental arm receiving FOLFOX in combination with Serplulimab and Bevacizumab.
Participants will undergo neoadjuvant treatment, surgical resection, and regular
follow-up assessments to evaluate treatment response, recurrence rates, and overall
survival. By comparing outcomes between the two groups, specifically assessing factors
like recurrence-free survival, overall survival, and changes in the immune
microenvironment, we aim to provide valuable insights into the optimization of treatment
strategies for this specific subset of colorectal cancer patients.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age ≥18 and ≤75 years old
- Histologically confirmed colorectal adenocarcinoma
- Radiological and/or pathological confirmation of liver metastases, with ≤5 lesions
- Genetic testing and/or immunohistochemistry confirmation of RAS, BRAF wild-type, and
pMMR/MSS
- Absence of extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary)
- Primary colorectal tumor has been or can be radically resected
- Liver metastatic lesions are resectable (including radiofrequency ablation and
SBRT), and postoperative NED (no evidence of disease) is expected. Resectable liver
metastases are specifically defined as ① ≤5 metastatic lesions; ② R0 resection can
be performed (including radiofrequency ablation and SBRT); ③ Sufficient residual
liver volume is expected after resection; ④ At least one hepatic vein can be
preserved after resection, with preserved blood flow in and out of the residual
liver and preserved bile ducts, and can preserve at least two adjacent liver
segments; ⑤ No extrahepatic metastases.
- No prior anti-tumor therapy for liver metastases, except for surgical resection of
primary lesions
- Normal hematological function (platelets >90×109/L; white blood cells >3×109/L;
neutrophils >1.5×109/L)
- Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminases ≤5 times
ULN, alkaline phosphatase ≤2.5 ULN, no ascites, normal coagulation function, albumin
≥35g/L
- Liver function classified as Child-Pugh grade A
- Serum creatinine below the upper limit of normal (ULN), or calculated creatinine
clearance rate >50ml/min (using Cockcroft-Gault formula)
- ECOG performance status 0-1
- Expected lifespan >3 months
- Signed written informed consent
- Willing and able to be followed up until death or end of study or study termination.
Exclusion Criteria:
- Diagnosis of colorectal cancer with distant extrahepatic metastases
- Prior chemotherapy, targeted therapy, intervention, or immunotherapy for liver
metastases
- No planned surgical resection for liver metastatic lesions
- Received oxaliplatin-containing adjuvant chemotherapy regimen within the past one
year
- Any toxicity residuals from previous chemotherapy, excluding alopecia, such as
peripheral neuropathy ≥NCI CTC v3.0 grade 2
- Use of immunosuppressive drugs one week prior to study treatment initiation,
excluding topical corticosteroids via nasal, inhalational, or other routes or
physiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/day of
prednisone or equivalent) or steroids used for prevention of contrast agent allergy
- Interstitial lung disease requiring corticosteroid treatment
- Known active autoimmune disease requiring symptomatic treatment or with a history of
such disease within the past 2 years. Patients with vitiligo, psoriasis, alopecia,
or Graves' disease who have not required systemic treatment within the past 2 years,
patients with hypothyroidism requiring only thyroid hormone replacement therapy, and
patients with type I diabetes requiring only insulin replacement therapy can be
included
- Known history of primary immunodeficiency
- Patients with active tuberculosis
- History of allogeneic organ or hematopoietic stem cell transplantation
- Known allergy to any monoclonal antibody or chemotherapy drug (Fluorouracil,
oxaliplatin) preparation or excipient component
- Bleeding tendency or coagulation disorder
- Significant symptoms of intestinal obstruction
- Hypertensive crisis or hypertensive encephalopathy
- Severe uncontrolled systemic complications such as infection or diabetes
- Clinically severe cardiovascular diseases such as cerebrovascular accident (within 6
months before enrollment), myocardial infarction (within 6 months before
enrollment), hypertension that remains uncontrolled after appropriate drug
treatment, unstable angina pectoris, congestive heart failure (NYHA 2-4), or
arrhythmia requiring medication
- Past or physical examination showing central nervous system diseases (such as
primary brain tumor, epilepsy uncontrolled by standard treatment, any history of
brain metastasis, or stroke)
- Diagnosis of other malignant tumors within the past 5 years (excluding basal cell
carcinoma and/or carcinoma in situ of the cervix after radical surgery)
- Patients who received any investigational drug therapy within the last 28 days prior
to the study
- Pregnant or lactating women and women of childbearing age not using or refusing to
use effective non-hormonal contraception (intrauterine devices, barrier
contraception combined with spermicidal gel, or sterilization surgery) or men with
reproductive potential unwilling or unable to comply with the study protocol
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510060
Country:
China
Status:
Recruiting
Contact:
Last name:
Yu-hong Li, MD, Ph D
Email:
liyh@sysucc.org.cn
Investigator:
Last name:
Yu-hong Li, MD, Ph D
Email:
Principal Investigator
Start date:
February 1, 2024
Completion date:
December 31, 2028
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/NCT06280495
