Phase II Clinical Study of Vitamin E Combined With Fruquintinib and Tislelizumab in Patients With Microsatellite Stabilized Metastatic Colorectal Cancer Who Failed Standard Therapy

Fudan University1 site in 1 country25 target enrollmentMarch 1, 2023

ConditionsColorectal Cancer Microsatellite Stable Colorectal Carcinoma

InterventionsVitamin E Fruquintinib Tislelizumab

DrugsVitamin E Fruquintinib Tislelizumab

Overview

Phase: Phase 2
Intervention: Vitamin E
Conditions: Colorectal Cancer
Sponsor: Fudan University
Enrollment: 25
Locations: 1
Primary Endpoint: objective response rate (ORR)
Status: Recruiting
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goal of this clinical trial is to learn about efficacy of Vitamin E in combination with Fuquinitinib and Tirelizumab in patients with microsatellite stabilized mCRC who have failed standard therapy. The main question is to explore the survival time, safety and tolerability of the treatment. At the same time, the correlation between biomarkers (including PD-L1 expression, tumor mutation load, lymphocyte subpopulation, cytokines, TCR, intestinal microbes, and others) and the efficacy and drug resistance mechanism will be analyzed, so as to provide reference for the subsequent guidance of the screening of benefit groups.

Detailed Description

Dietary supplements are commonly used during conventional cancer treatment. Vitamin E has a variety of functions, including enhancing immunity, anti-inflammation, and anti-oxidation. Tislelizumab is an anti-PD-1 monoclonal antibody, and furoquininib is a tyrosine kinase inhibitor that inhibits tumor angiogenesis. Studies have shown that immunotherapy combined with furoquininib has initial efficacy in the treatment of colorectal cancer. Whether vitamin E combined with immunotherapy and furoquininib can improve the prognosis of patients with colorectal cancer deserves to be studied. Therefore, the objective of this study is to evaluate the efficacy and safety of Vitamin E in combination with Fuquinitinib and Tirelizumab in patients with microsatellite stabilized mCRC who have failed standard therapy.

Registry

clinicaltrials.gov

Start Date

March 1, 2023

End Date

February 2027

Last Updated

10 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Fudan University

Responsible Party

Principal Investigator

Li Dawei

Professor

Fudan University

Eligibility Criteria

Inclusion Criteria

•Age ≥18 years old, both sexes;
•Patients with histologically or cytologically confirmed unresectable and metastatic CRC;
•Recist1.1-defined disease progression or intolerance to prior standard therapy during or after standard therapy. Standard therapy was required to include all the following agents: fluorouracilines, chemotherapy agents such as irinotecan, and oxaliplatin, with or without an anti-VEGF monoclonal antibody (e.g., bevacizumab). Left-sided KRAS/NRAS/BRAF wild-type subjects received combined anti-EGFR mAb (cetuximab or panitumumab).
•Before enrollment, the tumor tissue was pMMR by immunohistochemistry, or MSS or MSI-L by PCR or NGS;
•Patients with ECOG score of 0-1 and expected survival time ≥3 months, patients who can cooperate to observe adverse reactions and efficacy;
•At least one measurable tumor lesion according to RECIST 1.1 criteria;
•Good organ function:
•neutrophil ≥1.5\*109/L; Platelet ≥100\*109/L; Hemoglobin ≥9g/dl; Serum albumin ≥3g/dl;
•Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3 and T4 in the normal range;
•bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤ 2 times the upper limit of normal;

Exclusion Criteria

•Pathological diagnosis of other intestinal tumors, such as gastrointestinal stromal tumor;
•Tumor tissues were dMMR detected by immunohistochemistry, or MSI-H detected by PCR or NGS
•Prior treatment with PD-1 antibody, PD-L1 antibody, or CTLA-4 antibody;
•Previous or concurrent history of other malignant tumors, excluding adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
•Active autoimmune disease, history of autoimmune disease (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); It does not include autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type I diabetes on stable doses of insulin; Vitiligo or cured childhood asthma/allergy without any intervention in adulthood;
•A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation;
•Contraindications to antiangiogenic drugs (such as active bleeding, gastrointestinal bleeding, hemoptysis, etc.);
•History of interstitial lung disease (excluding radiation pneumonitis without steroid treatment) and non-infectious pneumonia;
•Patients with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
•The subject has active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit of the assay)