XELOX +Bev +Tislelizumab for First-line Treatment of MSS/pMMR RAS-mutated mCRC

XELOX and Bevacizumab in Combination With Tislelizumab for First-Line Treatment of Patients With MSS/pMMR RAS-mutated Metastatic Colorectal Cancer (mCRC): A Single-arm, Phase II Study.

The goal of this clinical trial is to compare XELOX +Bev +Tislelizumab with standard chemotherapy，in MSS/pMMR-type RAS-mutated metastatic colorectal adenocarcinoma. The main questions it aims to answer are efficacy and safety of the regimen of XELOX +Bev +Tislelizumab. The investigators want to transform ras-mutated colorectal cancer into a "hot tumor" through the combination of anti-vascular therapy and chemotherapy, and then achieve better therapeutic effect through the combination with immunotherapy. Participants will receive the regimen of XELOX +Bev +Tislelizumab.

Study Overview

• Status: Recruiting
• Conditions: Bevacizumab; Capecitabine; Metastatic Colorectal Cancer (mCRC); Oxaliplatin; Tislelizumab; First-Line; MSS/pMMR; RAS-mutated
• Intervention / Treatment: Drug: Tislelizumab+Bevacizumab+Oxaliplatin+Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Lin Yang
    • Contact: lin yang; Phone Number: 13611267380; Email: linyangcicams@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed initially unresectable MSS/pMMR-type RAS-mutant metastatic colorectal adenocarcinoma;
2. ECOG score of 0 or 1;
3. Ability to swallow oral medications;
4. Have at least one measurable lesion (according to RECIST v1.1 standard);
5. No anti-tumor treatment has been received after recurrence and metastasis;
6. Neoadjuvant or adjuvant chemotherapy containing fluorouracil drugs is allowed before or after radical resection of colorectal cancer, but the treatment needs to be completed for ≥ 6 months; if oxaliplatin is used in neoadjuvant or adjuvant chemotherapy, it includes The oxaliplatin regimen needs to be completed for ≥12 months;
7. Adequate organ function: On the premise of no component blood transfusion within 14 days: white blood cells ≥ 3.5*10^9/L and neutrophils ≥ 1.5*10^9/L, hemoglobin ≥ 90g/L, platelets ≥ 100* 10^9/L; serum bilirubin ≤ 1.5 times the normal value, alanine aminotransferase (ALT) ≤ 2.5 times the normal value, aspartate aminotransferase (AST) ≤ 2.5 times the normal value; Urinary protein <2+. Or urine protein 2+ but 24-hour urine protein quantity ≤ 1 g; serum creatinine ≤ 1.5 times of normal value, creatinine clearance rate ≥ 60ml/min; Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%);
8. Expected survival period ≥ 3 months;
9. Patients fully understand this research, voluntarily participate in this clinical trial and sign an informed consent;
10. Women with reproductive potential (< 2 years after the last menstrual period) and men use effective contraceptive methods until half a year after the last treatment.

Exclusion Criteria:

1. Previously received bevacizumab or anti-CTLA4, anti-PD-1/PD-L1 therapeutic antibodies or pathway-targeted drugs;
2. Received radiotherapy within 4 weeks before the evaluation;
3. Symptomatic peripheral neuropathy > grade 2 (CTCAE5.0 standard);
4. Received live vaccine or systemic immune stimulant (including but not limited to interferon or interleukin 2) within 1 month;
5. HIV-positive and other immunodeficiency diseases;
6. Active hepatitis B or hepatitis C (except for those who have been infected or cured before, that is, HBsAg negative and hepatitis B core antigen anti-HBc antibody positive; except for hepatitis C patients whose HCV RNA is negative by PCR);
7. Existing autoimmune diseases or other diseases that require immunosuppressant treatment, except for type 1 diabetes; except for hypothyroidism that only requires hormone replacement therapy; skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, alopecia areata); inhaled or topical steroids or equivalent steroids in excess of 10 mg prednisone per day, except for inactive autoimmune disease on adrenal replacement therapy;
8. Received systemic hormone therapy or treatment with a daily dose of more than 10 mg prednisone equivalent dose or other forms of immunosuppressive treatment within 7 days, but inhaled or topical steroids or daily application of more than 10 mg prednisone, etc. Except for inactive autoimmune diseases treated with adrenal replacement therapy with potent steroids;
9. Have a history of organ transplantation;
10. Uncontrolled central nervous system (CNC) metastasis (symptomatic or metastatic sites are midbrain, pons, medulla or spinal cord) or other central nervous system diseases;
11. Those who have undergone major surgery, open biopsy or obvious traumatic trauma within 1 month, or who may need major surgery during the study period; those who have undergone open biopsy or obvious traumatic trauma, or may need major surgery during the study period;
12. Combined with other malignant tumors other than intestinal cancer (except cured basal cell carcinoma or squamous cell carcinoma of the skin and carcinoma in situ of the cervix; the treatment of other malignant tumors has been completed for more than 1 year, and there is no clinical and imaging evidence of recurrence or progression except);
13. Combined active and refractory infection;
14. Cardiovascular diseases with clinical significance, such as cardiovascular accident (CVA) (≤ 6 months before treatment), myocardial infarction (≤ 6 months before treatment), unstable angina, chronic heart failure of NYHA ≥ 2 (CHF), uncontrolled arrhythmia; uncontrolled hypertension; thromboembolic or bleeding events within 6 months before treatment;
15. Evidence of causing coagulation disease;
16. With dysphagia, active peptic ulcer, complete or incomplete intestinal obstruction, active gastrointestinal bleeding, perforation, malabsorption syndrome or uncontrollable gastrointestinal inflammatory disease (such as Crohn's disease or ulcerative colon inflammation);
17. Severe unhealed wounds/ulcers or severe fractures;
18. Any serious acute or chronic medical condition that may affect the patient's participation in the study or interfere with the interpretation of the study results;
19. There are mental illnesses, serious social and psychological illnesses, or researchers believe that there are factors that may affect research compliance;
20. Pregnant or lactating women;
21. No therapeutic anticoagulant or antiplatelet drugs or NSAIDs (aspirin ≤ 325 mg/day allowed);
22. Severe allergic reaction to the test drug;
23. Reluctance to use alternative therapies such as (but not limited to) bisphosphonates if receiving RANKL inhibitors (eg, denosumab).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XELOX +Bev +Tislelizumab; Every 3 weeks as a cycle: Tislelizumab: 200mg, iv, d1;; Bevacizumab: 7.5mg/kg, iv, d1;; Oxaliplatin: 130mg/m2, iv, d1;; Capecitabine: 1000mg/m2, bid, po, d1-d14; Re-evaluate patients every two cycles. If the patient has been treated for more than 8 cycles, they will enter maintenance therapy, and the regimen is capecitabine + BEV combined with tislelizumab.	Drug: Tislelizumab+Bevacizumab+Oxaliplatin+Capecitabine; Use the above medications on a regular basis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR of regimen of XELOX +Bev +Tislelizumab	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)		2 years
Disease Control Rate (DCR);		2 years
Median Progression-Free Survival (mPFS)		2 years
12-month PFS rate		12 months
Median Overall Survival (mOS)		5 years
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Adverse Events (AEs) Incidence, Serious Adverse Events (SAE) Incidence	2 years

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: July 21, 2023
• First Posted (Actual): August 1, 2023

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Single-arm; Phase II
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab; Tislelizumab
• Other Study ID Numbers: NCC-009591

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No