Combining chemoradiotherapy with immunotherapy for advanced rectal cancer

A Series of Neoadjuvant Chemoradiotherapy Combined With Immunotherapy for Locally Advanced Rectal Cancer: From a Multicenter Phase II Cohort to a Phase III Randomized Controlled Study

This study is testing whether adding an immunotherapy drug to standard treatment can help people with advanced rectal cancer feel better and improve their quality of life.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 375 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing Friendship Hospital (Academic / other)
• Drugs / interventions: tislelizumab, chemotherapy, immunotherapy, prednisone, tirelizumab
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT06312982 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness and safety of combining neoadjuvant chemoradiotherapy with the immunotherapy drug tislelizumab compared to chemoradiotherapy alone in patients with locally advanced rectal cancer. Participants will undergo a structured treatment regimen that includes a long course of chemoradiotherapy followed by immunotherapy at specified intervals. The study will also assess the impact on quality of life and the retention of rectal or anal function. The trial is designed as a multicenter phase II cohort leading into a phase III randomized controlled study.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with pathologically confirmed rectal adenocarcinoma who have not received prior anti-tumor treatments.

Not a fit: Patients with a history of allergy to monoclonal antibodies or those who have previously received treatments for rectal cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and quality of life for patients with locally advanced rectal cancer.

How similar studies have performed: Other studies have shown promise in combining chemoradiotherapy with immunotherapy, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Signed a written informed consent form and volunteered to join the study;
2. .Age: 18-75 years old, male or female;
3. Pathohistologically confirmed rectal adenocarcinoma, along with immunohistochemical results of pMMR or genetic test results of MSS;
4. The baseline clinical stage assessed by MRI was T1-2N1-2M0 or T3N0-2M0, MRF (-), lateral lymph nodes (-);
5. The lower tumor margin is 10cm away from the anal margin;
6. Surgical resection;
7. Ability to swallow tablets normally;
8. ECOG PS 0-1；
9. Have not received any anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, surgery, etc.;
10. Plan to undergo surgery after the completion of the neoadjuvant therapy;
11. No contraindications to surgery;
12. Main organ function is normal.

Exclusion Criteria:

1. Previous history of allergy to monoclonal antibodies, any component of tislelizumab,and capecitabine;
2. Previously has received or is receiving any of the following treatments:

   A)Any tumor-specific surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc; B)Treatment with immunosuppressive drugs or systemic hormones within 2 weeks of first use (dose\> 10mg / day prednisone or equivalent dose); inhaled or topical steroids and dose\> 10mg / day prednisone or equivalent dose of adrenocorticoid replacement in the absence of active autoimmune disease; C)Having received a live attenuated vaccine within 4 weeks before the first use of the study drug; D)Major surgery or severe trauma within 4 weeks before the first use of study drug;
3. History of any active autoimmune or autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (considered after hormone replacement therapy); patients with psoriasis or asthma / allergy in childhood and adults without any intervention, but patients requiring medical intervention with bronchodilators should not be included;
4. A history of immunodeficiency, including a positive HIV test, or other acquired or congenital immunodeficiency disease, or a history of organ transplantation or allogeneic bone marrow transplantation;
5. Not well controlled cardiac clinical symptoms or disease, including but not limited to: such as (1) grade NYHA II above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, (4) clinical meaningful supraventricular or ventricular arrhythmia without clinical intervention or clinical intervention still poor control;
6. Severe infection (Grade CTCAE\> 2) within 4 weeks prior to the first use of study drug, Such as severe pneumonia, bacteremia, infection complications requiring hospitalization; Baseline chest imaging indicated the presence of active lung inflammation, presence of symptoms and signs and signs of infection within 14 days prior to the first administration of study drug or need for oral or intravenous antibiotics, Except for the preventive use of antibiotics; Found active tuberculosis infection by history or CT, Or those with a history of active tuberculosis infection within 1 year prior to enrollment, Or those with a history of active tuberculosis infection more than 1 year ago but without formal treatment;
7. Presence of active hepatitis B (HBV DNA 2000 IU / mL or 104copies / mL), hepatitis C (positive for hepatitis C antibody, and HCV RNA above the lower limit of detection of the analytical method);
8. A diagnosis of other malignancies within 5 years prior to the first use of study drug, unless a malignancy with low risk of metastasis or death (5-year survival\> 90%), such as adequately treated skin basal cell carcinoma or squamous cell carcinoma in situ, are considered;
9. Women in pregnancy or lactation;
10. Other factors, as judged by the investigator, may lead to forced termination of the study, such as other serious illness (including mental illness), alcohol, substance abuse, family or social factors, which may affect the safety or compliance of the subject.

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Beijing Friendship Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)
• Beijing Friendship Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Zhongtao Zhang, MD

Conditions Locally Advanced Rectal Carcinoma