Combining short-course radiation with immunotherapy for advanced rectal cancer

Total Neoadjuvant Therapy With Short-course Radiation Followed by Envafolimab Plus CAPEOX for MSS Locally Advanced Ultra Low Rectal Adenocarcinoma: An Prospective, Single Center, Single Arm Study

This study is testing a new treatment that combines short radiation, an immunotherapy drug, and chemotherapy to see if it helps people with advanced rectal cancer feel better and improve their outcomes.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sir Run Run Shaw Hospital (other)
• Drugs / interventions: immunotherapy, prednisone, chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05858567 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a new treatment approach for locally advanced ultra low rectal adenocarcinoma by combining short-course radiotherapy with the immunotherapy drug Envafolimab and CAPEOX chemotherapy. The goal is to evaluate the feasibility, efficacy, and safety of this combined treatment regimen while also identifying characteristics of patients who may benefit from it. The study will utilize multi-omics sequencing analysis to explore tumor and microenvironmental factors that could predict treatment outcomes. By developing an efficacy prediction model, the trial aims to optimize neoadjuvant therapy for this patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with locally advanced ultra low rectal adenocarcinoma who have not previously received anti-tumor or immunotherapy.

Not a fit: Patients with rectal cancer that is not classified as pMMR or MSS, or those who have already undergone anti-tumor or immunotherapy, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes and organ preservation for patients with advanced rectal cancer.

How similar studies have performed: While the combination of short-course radiation and immunotherapy is a novel approach, similar studies in other cancer types have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Patients who are willing to receive neoadjuvant therapy.
2. ≧18 years old.
3. Diagnosed by digital rectal examination, colonoscopy, and high-resolution MRI of the pelvis, the tumor is less than or equal to 5 cm from the anus.
4. Histologically diagnosed as rectal adenocarcinoma.
5. The clinical staging by pelvic contrast-enhanced CT and pelvic high-resolution MRI were stage I, II and III.
6. MMR protein detection or MSI gene detection of rectal cancer specimens confirmed pMMR or MSS before treatment .
7. The patient is difficult cured by anal reserve procedure based on the primary physician's practice.
8. The patient has good compliance and can come to the hospital for re-examination as required.
9. ECOG Scale of Performance Status score 0-1 point.
10. Have not received anti-tumor and immunotherapy before enrollment.
11. Laboratory inspections must meet the following standards:

1) White blood cell count\>3.5×109/L, absolute value of neutrophils\>1.8×109/L, platelet count ≥75×109/L, hemoglobin ≥100g/L; 2) INR≤1.5, and APTT≤1.5 times the upper limit of normal or partial prothrombin time (PT) ≤1.5 times the upper limit of normal; 3) Total bilirubin ≤ 1.25 times the upper limit of normal; ALT and AST \< 5 times the upper limit of normal; 4) 24h creatinine clearance \>50mL/min or serum creatinine \<1.5 times the upper limit of normal.

12. Voluntarily participate in this study and sign the informed consent.

Exclusion Criteria:

1. History of other malignant diseases in the past 5 years.
2. Patients with metastases from other sites (stage IV patients).
3. Patients with positive lateral lymph nodes by pelvic contrast-enhanced CT and pelvic high-resolution MRI.
4. Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. requiring emergency surgery.
5. Known allergic to oxaliplatin, capecitabine, PD-L1 monoclonal antibody and other drugs.
6. Pathologically suggested signet ring cell carcinoma and mucinous adenocarcinoma.
7. dMMR or MSI-H patients.
8. The patient is accompanied by any unstable systemic disease, including but not limited to: severe infection, uncontrolled diabetes, hypertension uncontrolled by medication, unstable angina, cerebrovascular accident or transient cerebral ischemia, myocardial Infarction, congestive heart failure, severe cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease; disease affecting the patient's life.
9. The disease (such as mental illness, etc.) or condition (such as alcoholism or drug abuse, etc.) associated with the patient will increase the risk of the patient receiving the trial drug treatment or affect the patient's compliance with the trial requirements, or may confuse the research results.
10. Active autoimmune disease that may worsen while receiving immunostimulants.
11. Known history of positive HIV test or known acquired immunodeficiency syndrome.
12. Patients who are using immunosuppressive agents, except for the following conditions:

1) Intranasal, inhaled, topical steroids, or topical steroid injections (eg, intra-articular injections); 2) Physiological doses of systemic corticosteroids ≤10 mg/day prednisone or equivalent; 3) Steroids used to prevent allergic reactions (eg, before CT scan). 13. Received any other experimental drug treatment or participated in another interventional clinical trial within 30 days before screening 14. Women who are pregnant or breastfeeding or who plan to become pregnant or breastfeeding during the study period; men or women who are unwilling to take effective contraceptive measures.

15. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, etc.

16. Other conditions that the investigator judges that the patient is not suitable to participate in the clinical study, etc.

Where this trial is running

Hangzhou, Zhejiang

• Sir Run Run Shaw Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: sheng dai, MD&PhD

Conditions: Rectal Cancer