Clinical trial NCT06282445: Efficacy and Safety of Chemotherapy With XELOX (Oxaliplatin + Capecitabine) and Bevacizumab in Combination With Adebrelimab in First-line Treatment of Microsatellite Stable (MSS) Initially Unresectable Metastatic Colorectal Cancer
Official title: Efficacy and Safety of Chemotherapy With XELOX (Oxaliplatin + Capecitabine) and Bevacizumab in Combination With Adebrelimab in First-line Treatment of Microsatellite Stable (MSS) Initially Unresectable Metastatic Colorectal Cancer: a Prospective, Multicenter, Single-arm Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Lead sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of Chemotherapy With XELOX (Oxaliplatin + Capecitabine) and Bevacizumab in Combination With Adebrelimab in First-line Treatment of Microsatellite Stable (MSS) Initially Unresectable Metastatic Colorectal Cancer.

Detailed description: At present, the survival benefit of MSS mCRC patients is limited, and the general survival time is only about 3-4 months. Up to now, the standard treatment plan is FOLFOX combined with bevacizumab. AtezoTRIBE study shows that compared with FOLFOXIRI+ bevacizumab, the standard treatment plan is better than the standard treatment plan. The combination of PD-L1 monomone attillizumab extended mPFS from 11.4 months to 12.9 months, showing certain efficacy, and the combination of Attillizumab did not increase adverse reactions. Based on the above, this study aims to explore the efficacy and safety of chemotherapy with XELOX (oxaliplatin + capecitabine) regimen and bevacizumab combined with adbelizumab in first-line treatment of microsatellite stable (MSS) type of initial unresectable metastatic colorectal cancer.

Eligibility criteria: Inclusion Criteria:

* 1.The patients voluntarily participated in the study, signed the informed consent, and had good compliance.
* 2. Age 18-75 years (including 18 and 75) .
* 3. Metastatic colorectal cancer confirmed histologically and/or cytologically and initially unresectable.
* 4.MSS or pMMR.
* 5.Patients must have at least one measurable lesion (RECIST 1.1).
* 6.ECOG physical condition 0-1 score.
* 7.Expected survival ≥12 weeks.
* 8.Blood examination (no blood transfusion within 14 days, no correction of granulocyte colony stimulating factor or other hematopoietic stimulating factor within 7 days before laboratory examination).

  1. neutrophil absolute value ≥1.5×109/L, platelets ≥100×109/L, hemoglobin concentration ≥9g/dL)
  2. Liver function test (bilirubin ≤1.5×ULN; Aspartate aminotransferase and glutamic acid aminotransferase ≤2.5×ULN, AST and ALT≤5×ULN in the case of liver metastasis);
  3. Renal function (serum creatinine ≤1.5×ULN, or creatinine clearance (CCr)≥60ml/min);
  4. Coagulation, International standardized ratio (INR) ≤1.5×ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN;
  5. Thyroid function, thyroid stimulating hormone (TSH) ≤ the upper limit of normal (ULN); If there is any abnormality, FT3 and FT4 levels should be examined. If FT3 and FT4 levels are normal, they can be selected.
* 9.Reproductive-age women must have a negative serum pregnancy test within 14 days before treatment and be willing to use a medically acceptable effective contraceptive method (e.g., an intrauterine device, oral contraceptives, or condoms) during the study and for 3 months after the last study dose; for male subjects who are married to a reproductive-age woman, surgical sterilization is required or effective contraception is recommended during the study and for 3 months after the last study dose.

Exclusion Criteria:

* 1.Received the following treatments within 4 weeks prior to treatment: radiotherapy for tumors, surgery, chemotherapy, immunotherapy or molecular targeted therapy, or other investigational medications.
* 2.Active autoimmune disease requiring systemic therapy (i.e., disease-modifying drugs, corticosteroids, or immunosuppressants) has been used within the past 2 years. Replacement therapies (such as thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic therapy.
* 3.Diagnosed with an immune deficiency within 7 days prior to the first treatment or received systemic steroid therapy or any other form of immunosuppressive therapy. The use of physiological doses of corticosteroids may be approved after consultation with the sponsor.
* 4.Previously received anti-vascular small-molecule targeted drug therapy, such as fuquintinib.
* 5.Previous treatment with irinotecan based chemotherapy regimens.
* 6.Symptomatic brain or meningeal metastasis.
* 7.RAS wild-type left half colon cancer.
* 8.Metastatic colorectal cancer with MSI-H or dMMR.
* 9.Severe infection (such as intravenously administered antibiotics, antifungals, or antivirals) within 4 weeks of treatment, or unexplained fever \> 38.5 ° C during screening/first administration.
* 10.Have high blood pressure that is not well controlled with antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
* 11.There were obvious clinical bleeding symptoms or obvious bleeding tendency within 3 months before treatment (bleeding \> 30 mL within 3 months, hematemesis, black stool, blood in the stool), hemoptysis (\> 5 mL of fresh blood within 4 weeks), etc. Or treatment of venous/venous thrombosis events within the preceding 6 months, such as cerebrovascular accidents (including transient ischemic episodes, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; Long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day) is required.
* 12.During screening, it was found that the tumor invaded large vascular structures, such as pulmonary artery, superior vena cava or inferior vena cava, etc., and the researchers judged that there was a risk of major bleeding.
* 13.Active heart disease, including myocardial infarction, severe/unstable angina, occurred 6 months before treatment. Left ventricular ejection fraction \<50% by echocardiography showed poor arrhythmia control.
* 14.Patients have had other malignancies (except cured basal cell carcinoma of the skin and cervical carcinoma in situ) within the previous 5 years or at the same time.
* 15.Is known to be allergic to the investigational drug or any of its excipients.
* 16.Active or uncontrolled severe infection.

  1. Known human immunodeficiency virus (HIV) infection.
  2. Known history of clinically significant liver disease, including viral hepatitis \[active HBV infection, i.e., positive HBV DNA (\>1×104 copies /mL or \>2000IU/ml) must be excluded for known hepatitis B virus (HBV) carriers.
  3. Known hepatitis C virus infection (HCV) and HCV RNA positive (\>1×103 copies /mL), or other hepatitis, cirrhosis\]

Primary outcomes:
measure: Progression-free survival
timeFrame: Up to 2 years
Secondary outcomes:
measure: Organ retention rate
timeFrame: Up to 2 years
measure: Overall survival
timeFrame: Up to 2 years
measure: Disease Control Rate
timeFrame: Up to 2 years
measure: Surgical conversion rate
timeFrame: Up to 2 years
measure: TRAEs
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Jinhua
country: China
facility: The Fourth Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: China, The Fourth Affiliated Hospital Zhejiang University School of Medicine
name: Dezhi Li, MD&PhD
role: PRINCIPAL_INVESTIGATOR
References: