Trial Title:
Vitamin E Combined With Fruquintinib and Tislelizumab in Microsatellite Stabilized Metastatic Colorectal Cancer Patients
NCT ID:
NCT05771181
Condition:
Colorectal Cancer
Microsatellite Stable Colorectal Carcinoma
Conditions: Official terms:
Colorectal Neoplasms
Vitamin E
Tislelizumab
Conditions: Keywords:
Tirelizumab
Fuquinitinib
Vitamin E
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Vitamin E
Description:
Vitamin E: 400mg (QD), oral, once daily, continued until disease progression or
intolerable toxicity.
Arm group label:
Vitamin E in combination with Fuquinitinib and Tislelizumab
Intervention type:
Drug
Intervention name:
Fruquintinib
Description:
Fuquinitinib: 5mg (QD) orally for 2 weeks, 1 week off, repeated every 3 weeks until
disease progression or intolerable toxicity.
Arm group label:
Vitamin E in combination with Fuquinitinib and Tislelizumab
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
Tislelizumab: 200mg intravenously every 3 weeks (Q3W), was administered until the
occurrence of unacceptable toxic effects, or disease progression, withdrawal of consent,
or withdrawal as judged by the investigator.
Arm group label:
Vitamin E in combination with Fuquinitinib and Tislelizumab
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years old, both sexes;
2. Patients with histologically or cytologically confirmed unresectable and metastatic
CRC;
3. 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).
4. Before enrollment, the tumor tissue was pMMR by immunohistochemistry, or MSS or
MSI-L by PCR or NGS;
5. Patients with ECOG score of 0-1 and expected survival time ≥3 months, patients who
can cooperate to observe adverse reactions and efficacy;
6. At least one measurable tumor lesion according to RECIST 1.1 criteria;
7. Good organ function:
1. neutrophil ≥1.5*109/L; Platelet ≥100*109/L; Hemoglobin ≥9g/dl; Serum albumin
≥3g/dl;
2. Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3 and
T4 in the normal range;
3. bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤ 2 times the
upper limit of normal;
4. Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance
≥60ml/min;
5. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the
upper limit of the normal range, unless the patient is receiving anticoagulant
therapy and the PT value is within the intended range for anticoagulant
therapy;
6. Activated partial thromboplastin time (aPTT) ≤ 1.5 times the upper limit of
normal;
8. There were no serious concomitant diseases that could make the survival time less
than 5 years;
9. Negative pregnancy test in female subjects (for female patients of childbearing
potential); Infertile female patients;
10. Male patients of childbearing potential and female patients of childbearing
potential and at risk of pregnancy must agree to use adequate contraception for the
entire duration of the study and for 12 months after receiving treatment with the
protocol;
11. Signed and dated informed consent indicating that the patient has been informed
about all relevant aspects of the study;
12. Patients who are willing and able to comply with the visit schedule, treatment plan,
laboratory tests, and other study procedures;
13. Willing to comply with the arrangement during the study period can not participate
in any other clinical research on drugs and medical devices.
Exclusion Criteria:
1. Pathological diagnosis of other intestinal tumors, such as gastrointestinal stromal
tumor;
2. Tumor tissues were dMMR detected by immunohistochemistry, or MSI-H detected by PCR
or NGS
3. Prior treatment with PD-1 antibody, PD-L1 antibody, or CTLA-4 antibody;
4. Previous or concurrent history of other malignant tumors, excluding adequately
treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary
carcinoma;
5. 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;
6. A history of immunodeficiency, including HIV positive, other acquired or congenital
immunodeficiency diseases, or organ transplantation or allogeneic bone marrow
transplantation;
7. Contraindications to antiangiogenic drugs (such as active bleeding, gastrointestinal
bleeding, hemoptysis, etc.);
8. History of interstitial lung disease (excluding radiation pneumonitis without
steroid treatment) and non-infectious pneumonia;
9. 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;
10. 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)
11. Severe cardiopulmonary and renal dysfunction;
12. Have hypertension that is not well controlled with antihypertensive medication
(systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
13. A history of psychotropic substance abuse, alcohol or drug abuse;
14. Other factors that may affect subject safety or trial compliance as judged by the
investigator. Severe medical conditions requiring concomitant treatment (including
mental illness), serious laboratory abnormalities, or other family or social
factors.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
270 Dongan Road, Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Contact:
Last name:
Dawei Li, PhD
Phone:
+8613774201693
Email:
li_dawei@fudan.edu.cn
Contact backup:
Last name:
Zhiyu Chen, PhD
Phone:
+8618721841159
Email:
chanhj@aliyun.com
Start date:
March 2023
Completion date:
February 2027
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05771181
