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

NCT05970302 | Recruiting Phase 2

• 1 other identifier: NCC-009591
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tislelizumab; Bevacizumab; Oxaliplatin; Capecitabine; MSS/pMMR; Metastatic Colorectal Cancer (mCRC); RAS-mutated; First-Line

Keywords

Single-arm; Phase II

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR of regimen of XELOX +Bev +Tislelizumab

  2 years

Secondary Outcomes (6)

• 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

Study Arms (1)

XELOX +Bev +Tislelizumab

EXPERIMENTAL

Every 3 weeks as a cycle: 1. Tislelizumab: 200mg, iv, d1; 2. Bevacizumab: 7.5mg/kg, iv, d1; 3. Oxaliplatin: 130mg/m2, iv, d1; 4. 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

Interventions

Tislelizumab+Bevacizumab+Oxaliplatin+Capecitabine DRUG

Use the above medications on a regular basis.

XELOX +Bev +Tislelizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed initially unresectable MSS/pMMR-type RAS-mutant metastatic colorectal adenocarcinoma;
• ECOG score of 0 or 1;
• Ability to swallow oral medications;
• Have at least one measurable lesion (according to RECIST v1.1 standard);
• No anti-tumor treatment has been received after recurrence and metastasis;
• 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;
• 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%);
• Expected survival period ≥ 3 months;
• Patients fully understand this research, voluntarily participate in this clinical trial and sign an informed consent;
• 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.

You may not qualify if:

• Previously received bevacizumab or anti-CTLA4, anti-PD-1/PD-L1 therapeutic antibodies or pathway-targeted drugs;
• Received radiotherapy within 4 weeks before the evaluation;
• Symptomatic peripheral neuropathy \> grade 2 (CTCAE5.0 standard);
• Received live vaccine or systemic immune stimulant (including but not limited to interferon or interleukin 2) within 1 month;
• HIV-positive and other immunodeficiency diseases;
• 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);
• 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;
• 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;
• Have a history of organ transplantation;
• Uncontrolled central nervous system (CNC) metastasis (symptomatic or metastatic sites are midbrain, pons, medulla or spinal cord) or other central nervous system diseases;
• 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;
• 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);
• Combined active and refractory infection;
• 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;
• Evidence of causing coagulation disease;

Sponsors & Collaborators

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

Study Sites (1)

Lin Yang

Beijing, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: July 6, 2023
• First Posted: August 1, 2023
• Study Start: July 7, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

CN (1)