Vitamin E plus fruquintinib and tislelizumab for microsatellite-stable metastatic colorectal cancer

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

This trial tests whether adding vitamin E to fruquintinib and tislelizumab helps people with microsatellite-stable metastatic colorectal cancer who have not responded to standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: bevacizumab, cetuximab, panitumumab, chemotherapy, radiation, Tirelizumab, Fuquinitinib, Tislelizumab, furoquininib, immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05771181 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center interventional trial at Fudan University Shanghai Cancer Center gives patients with pMMR/MSS metastatic colorectal cancer a combination of vitamin E, the VEGFR inhibitor fruquintinib, and the anti–PD-1 antibody tislelizumab. Eligible patients have progressed on standard chemotherapy (fluoropyrimidines, irinotecan, oxaliplatin) with or without anti-VEGF therapy and must have measurable disease and ECOG 0–1. The study will monitor safety, tolerability, and survival outcomes while regularly imaging tumors per RECIST 1.1. Parallel biomarker analyses (PD-L1, tumor mutation burden, lymphocyte subsets, cytokines, TCR repertoire, gut microbiome, and others) will be correlated with responses and mechanisms of resistance.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable or metastatic pMMR/MSS colorectal cancer who progressed on standard regimens, have at least one measurable lesion, and have ECOG performance status 0–1 are the intended candidates.

Not a fit: Patients with MSI-high tumors, ECOG >1, significant organ dysfunction, lack of measurable disease, or those who have not yet received required prior standard therapies are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could improve response rates or extend survival for patients with MSS metastatic colorectal cancer who have exhausted standard therapies.

How similar studies have performed: Immunotherapy combined with anti-angiogenic agents has shown preliminary activity in colorectal cancer, but adding vitamin E is a novel component with limited prior clinical data.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• 270 Dongan Road, Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Dawei Li, PhD — Fudan University
• Study coordinator: Dawei Li, PhD

Conditions Colorectal Cancer; Microsatellite Stable Colorectal Carcinoma; Tirelizumab; Fuquinitinib; Vitamin E