Neoadjuvant treatment for local advanced rectal cancer using a PD-1 inhibitor and chemoradiotherapy

Neoadjuvant Preoperative Arterial Intervention With Concurrent Chemoradiotherapy in Local Advanced Rectal Cancer

This study is testing a new treatment for local advanced rectal cancer that combines a special drug and chemotherapy before surgery to see if it works better than standard options for patients who haven't had these treatments before.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Third Military Medical University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, Tirellizumab
• Locations: 1 site (Chongqing, Chongqing Municipality)
• Trial ID: NCT05957016 on ClinicalTrials.gov

What this trial studies

This study aims to enhance the effectiveness of neoadjuvant therapy for local advanced rectal cancer (LARC) by utilizing a combination of preoperative arterial infusion of Tirellizumab, a PD-1 inhibitor, and oxaliplatin, followed by tumor artery embolization and concurrent chemoradiotherapy. The approach is based on previous research that demonstrated the potential benefits of arterial chemo-immuno-embolization in treating LARC. The study will evaluate the safety and efficacy of this novel regimen in patients who have not previously undergone chemotherapy or radiation therapy.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with locally advanced rectal cancer who have not received prior chemotherapy or radiation.

Not a fit: Patients with severe allergic reactions to humanized antibodies or those who have previously undergone chemotherapy or radiation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with local advanced rectal cancer.

How similar studies have performed: Previous studies exploring similar approaches have shown promising results, indicating potential efficacy in treating locally advanced rectal cancer.

Eligibility criteria

Inclusion Criteria:

* Local advanced Rectal cancer: stage T3/4NanyM0 or T1-2N+M0.
* Ages: 18 to 75.
* No previously received chemotherapy drugs and radiation therapy.
* ECOG score: 0 - 2.
* Appropriate organ function, as defined below:

(Hematology and blood biochemistry examination must be completed within 7 days before the registration date) i) White blood cell count ≥ 4,000/mm3. ii) Neutrophil count ≥ 1,500/mm3. iii) Hemoglobin ≥ 10 g/dL. iv) Platelet count ≥ 100,000/mm3. v) Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). vi. Liver function Index (AST \& ALT) ≤ 1.5 times the upper limit of normal (ULN).

vii. Serum creatinine ≤1.5 times the upper limit of normal or creatinine clearance ≥60 ml/min.

* Tolerance of orally administration of capecitabine.
* Can understand the study, have good compliance, cooperate with follow-up.

Exclusion Criteria:

* Severe allergic reaction to humanized antibodies or fusion proteins;
* Hypersensitivity to any component contained in contrast agent or granule embolic agent;
* Diagnosed with an immune deficiency or is receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 14 days prior to the first administration of the study, allowing the use of physiological doses of glucocorticoids (≤10mg/ day of prednisone or equivalent);
* Active, known, or suspected autoimmune diseases (such as interstitial pneumonia, colitis, hepatitis, pituitaritis, vasculitis, nephritis, hypothyroidism, including, but not limited to, these diseases or syndromes). Subjects who have type 1 diabetes, hypothyroidism requiring hormone replacement therapy, skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis, or hair loss), or conditions that are not expected to recur in the absence of external triggers may be enrolled;
* Pre-existing severe heart disease, including congestive heart failure, uncontrolled high-risk arrhythmias, unstable angina pectoris, myocardial infarction, and severe heart valve disease;
* Active hepatitis B (HBV DNA ≥ 2000IU/ml or 104copies/ml), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the lower limit of analysis).
* Active tuberculosis (TB) infection. Patients with a history of active tuberculosis infection within the previous 1 year should be excluded, even if they have been treated; Patients with a history of active tuberculosis infection more than 1 year ago should also be excluded unless the duration and type of antituberculosis therapy previously used is demonstrated to be appropriate.
* Brain metastases accompanied by symptoms or symptoms controlled for less than 2 months;
* Received major surgical treatment, open biopsy, or significant traumatic injury within 28 days prior to enrollment;
* Pregnant or lactating female patients (women of childbearing age must confirm that the pregnancy test is negative within 7 days before the first administration of the drug, if it is positive, ultrasound examination must be performed to rule out pregnancy), subjects of childbearing age refuse to accept contraceptive measures; Combined with other malignancies, except cured skin basal cell carcinoma or skin squamous cell carcinoma or in situ carcinoma of any other site
* Patients with any physical signs or history of bleeding, regardless of severity; Non-healing wounds, ulcers, or fractures were present in patients with any bleeding or bleeding events ≥CTCAE grade 3 during the 4 weeks prior to grouping;
* Arteriovenous thrombosis events within 6 months, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism;
* Dementia, altered mental status or any mental illness that would prevent understanding or giving informed consent or completing the questionnaire
* Other serious concomitant diseases judged by the investigator.

Where this trial is running

Chongqing, Chongqing Municipality

• Daping Hospital, Third Military Medical University — Chongqing, Chongqing Municipality, China (Recruiting)

Conditions Rectal Cancer; local advanced rectal cancer; PD-1 inhibitor; neoadjuvant