Trial Title:
First-Line Treatment Induced With mFOLFOX6 and HLX04 Regimen, Following Combined With Serplulimab in MSS Initially Unresectable Metastatic Colorectal Cancer
NCT ID:
NCT06491355
Condition:
Efficacy, Self
Safety Issues
Colo-rectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
mfolfox6 and hlx04 regimen and Serplulimab
Description:
mfolfox6 and hlx04 regimen induction therapy followed by combined treatment with
slulimumab in the experimental arm. In the active comparator. only with mfolfox6 and
hlx04 regimen treatment.
Arm group label:
mfolfox6 and hlx04 regimen induction therapy followed by combined treatment with slulimumab
Intervention type:
Drug
Intervention name:
mfolfox6 and hlx04 regimen
Description:
In the active comparator. only with mfolfox6 and hlx04 regimen treatment.
Arm group label:
mfolfox6 and hlx04 regimen treatment
Summary:
This is a prospective, multi-center, randomized controlled clinical intervention study,
aiming to explore the effectiveness and safety of mfolfox6 and hlx04 regimens combined
with slulimumab as first-line treatment for MSS-type initial unresectable metastatic
colorectal cancer after induction therapy. This study plans to include a total of 72
patients with untreated MSS-type initial unresectable metastatic colorectal cancer.
This study randomly allocated groups through a randomization system, and entered the
following treatment groups at a ratio of 1:1: (1) Experimental group: mfolfox6 and hlx04
regimen induction therapy followed by slulimab treatment (36 cases); (2) Control group
Group: mfolfox6 and hlx04 regimen treatment (36 cases).
Detailed description:
Colorectal Cancer (CRC) is a common malignant tumor. Its incidence ranks third and second
among men and women respectively, and its mortality rate ranks third. Data from the World
Health Organization's International Agency for Research on Cancer (IARC) in 2020 show
that more than 930,000 patients died due to CRC. Since 2000, the incidence and mortality
of colorectal cancer have been steadily increasing in China. The National Cancer Center
of China (NCC) reported that there were approximately 408,000 new cases of CRC in China
in 2016, and approximately 196,000 deaths. Most of the patients are in the mid-to-late
stage when diagnosed, and about 35% of them are in the advanced stage. They have no
chance of radical surgery and can only receive palliative care.
In the early days when leucovorin (LV) and 5-fluorouracil (5-FU) were used as the main
treatment options for patients with metastatic colorectal cancer (mCRC), the efficacy was
poor, and the median overall survival (OS) of patients was only for 8-12 months. Since
the introduction of effective cytotoxic drugs such as irinotecan and oxaliplatin in 2000,
the combination regimens FOLFOX (5-FU/LV + oxaliplatin) and FOLFIRI (5-FU/LV +
irinotecan) have become first-line systemic Standard protocol in treatment. The use of
biologics targeting key pathways in the development and progression of mCRC, such as
epidermal growth factor receptor (EGFR) and vascular endothelial growth factor
(VEGF)-related pathways, further extends the survival of mCRC patients.
In the latest version of CSCO colorectal cancer diagnosis and treatment guidelines, the
main recommended first-line treatments are FOLFOX/FOLFIRI±bevacizumab or cetuximab (both
RAS and BRAF are wild-type), FOLFOX/FOLFIRI±bevacizumab (RAS or BRAF mutant).
PD-1 plays an important role in suppressing immune responses and promoting immune
tolerance by inhibiting the activity of T cells, allowing cancer cells to evade immune
surveillance. Cells in the tumor microenvironment often express PD-1 and PD-L1.
Consistent with the inducible expression of PD-L1 by tumor cells, activated CD8+ effector
T cells often express PD-1, indicating that tumor cells are resistant to adaptive immune
responses. PD-L1 has been found to be expressed in many types of cancer, including
melanoma, lung cancer, urothelial cancer, and hepatocellular carcinoma. Its expression
can also be induced by various factors such as radiation, which helps cancer cells evade
immune regulation. Blocking the PD-1/PD-L1 interaction has been shown to treat a variety
of cancers. Clinical studies have proven that anti-PD-1 and anti-PD-L1 monoclonal
antibodies can induce long-lasting anti-tumor activity against a variety of tumors.
Anti-PD-1 monoclonal antibodies have been approved for the treatment of melanoma,
non-small cell lung cancer, small cell lung cancer, head and neck squamous cell
carcinoma, urothelial carcinoma, entities with high microsatellite instability or
mismatch repair deficiency and colorectal cancer, gastric cancer, esophageal cancer,
cervical cancer, hepatocellular carcinoma (HCC), Merkel cell carcinoma (MCC), renal cell
carcinoma, endometrial cancer, bladder cancer, primary mediastinal large B-cell lymphoma
( PMBCL) and classic Hodgkin lymphoma. A large number of clinical studies of anti-PD-1
antibodies are currently underway, some as monotherapy and some in combination with
multiple drugs.
This study is an open-label, single-arm, phase II clinical trial. The study inclusion
criteria are patients with unresectable mCRC aged 18-75 years old and histologically
confirmed by multidisciplinary treatment (MDT). The patients have RAS gene mutations and
are confirmed to be MSS. state. All patients received treatment with sintilimab combined
with CapeOx and bevacizumab. After the disease achieved complete response (CR)/partial
response (PR)/stable disease (SD), maintenance treatment was performed. The main purpose
of the study Endpoints include objective response rate (ORR) as assessed by RECIST v1.1
and adverse events as assessed by CTCAE v5.0. The secondary endpoint is progression-free
survival (PFS).
This study mainly aims to explore the effectiveness of chemotherapy and bevacizumab
induction therapy combined with PD-1 monoclonal antibody in the first-line treatment of
MSS-type initial unresectable metastatic colorectal cancer. The second is its safety and
tolerability.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patient volunteered to participate in the study, signed the informed consent
form, and had good compliance.
2. Age: 18-75 years old (including 18 years old and 75 years old).
3. Body weight of 40kg.
4. Metastatic colorectal cancer confirmed by histology and / or cytology and initially
unresectable.
5. MSS type or pMMR.
6. Patients are required to have at least one measurable lesion (RECIST 1.1).
7. ECOG physical strength status: 0-1 point.
8. Expected survival of 12 weeks.
9. Blood test (no transfusion within 14 days, no correction with granulocyte colony
stimulating factor or other hematopoietic stimulating factor within 7 days before
the laboratory test)
1. Absolute neutrophil value of 1.5109/ L, platelet 1010109/ L, hemoglobin
concentration of 9 g/dL);
2. Liver function test (bilirubin 1.5 ULN; aspartate aminase and glutamate aminase
2.5 ULN, AST and ALT 5 ULN);
3. Renal function (serum creatinine 1.5 ULN or creatinine clearance (CCr) 60
mL/min);
4. Coagulation (international normalized ratio (INR) 1.5 ULN, prothrombin time
(PT) and activated partial thromboplastin time (APTT) 1.5 ULN);
5. Thyroid function, upper limit of normal (TSH); if abnormal, FT3 and FT4 levels
should be examined, normal FT3 and FT4 levels can be included.
10. Women of childbearing age must have a negative serum pregnancy test within 14 days
before treatment and be willing to use medically approved effective contraception
(e. g., IU, contraceptives or condoms) during 3 months after the study and the last
study drug; surgical sterilization for male subjects with a woman of childbearing
age, or effective contraception is recommended during the study and 3 months after
the last study dose.
Exclusion Criteria:
1. Have received the following treatments within the first 4 weeks of treatment: tumor
radiotherapy, surgery, chemotherapy, immune or molecular targeted therapy, and other
clinical study drugs.
2. Active autoimmune diseases requiring systemic treatment (i. e., corticosteroids or
immunosuppressive agents) have occurred in the past 2 years. Alternative therapies
(such as thyroxine, insulin, or physiological corticosteroid replacement therapy for
adrenal or pituitary insufficiency, etc.) are not considered systemic treatment.
3. Diagnosis with immunodeficiency or receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first treatment. A
physiological dose of corticosteroids may be approved after consultation with the
investigator.
4. Previous small molecule targeted drug therapy, such as fuquintinib, etc.
5. Previous treatment with an oxaliplatin-based chemotherapy regimen.
6. Symptomatic brain or meningeal metastases.
7. Metastatic colorectal cancer with either MSI-H or dMMR.
8. Severe infection (e. g. intravenous infusion of antibiotics, antifungals or
antiviral drugs), or unexplained fever> 38.5℃ during screening / first dose.
9. Hypertension that is not well controlled with antihypertensive medication (systolic
140 mmHg or diastolic 90 mmHg).
10. Significant clinical bleeding symptoms or significant bleeding tendency (bleeding>
30 mL, hematemesis, black feces, stool within 3 months), hemoptysis (> 5 mL of fresh
blood within 4 weeks); or venous / venous thrombosis events within 6 months, such as
cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage,
cerebral infarction), deep vein thrombosis and pulmonary embolism; or long-term
anticoagulation with Chinese standard or heparin, or long-term antiplatelet therapy
(aspirin 300 mg / day or clopidogrel 75 mg / day).
11. During screening, the tumor was found to invade large vascular structures, such as
pulmonary artery, superior vena cava vein or inferior vena cava vein, which was
judged to be at risk of large bleeding by the investigators.
12. Active heart disease, including myocardial infarction, severe / unstable angina,
within 6 months before treatment. Echocardiography showed a left ventricular
ejection fraction of <50%, and the arrhythmia was poorly controlled.
13. Other malignancies within or during the previous 5 years (except for cured skin
basal cell carcinoma and carcinoma of the cervix in situ).
14. Known allergy to the study drug or any of its excipients.
15. Active or uncontrolled serious infection; A)known human immunodeficiency virus (HIV)
infection; B) known history of clinically significant liver disease, including:
viral hepatitis [known hepatitis B virus (HBV) carriers must exclude active HBV
infection, namely HBV DNA positive (> 1104 copies / mL or> 2000 IU / mL); known
hepatitis C virus infection (HCV) and HCV RNA positive (> 1103 copies / mL)], or
other hepatitis, cirrhosis;
16. Any other disease, clinically significant metabolic abnormalities abnormal physical
examination or laboratory abnormalities, according to the investigator, there is
reason to suspect a disease or state is not suitable for the study drug (such as
seizures and need treatment), or will affect the interpretation of the results, or
make the patient in a high risk situation.
17. Routine urine indicates urine protein 2 +, and 24-hour urine protein quantification>
1.0g.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sir Run Run Shao hospital
Address:
City:
Hanzhou
Zip:
310016
Country:
China
Start date:
July 1, 2024
Completion date:
June 30, 2026
Lead sponsor:
Agency:
Sir Run Run Shaw Hospital
Agency class:
Other
Source:
Sir Run Run Shaw Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06491355
