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
Overview
- Phase
- Phase 2
- Intervention
- Envafolimab
- Conditions
- Rectal Cancer
- Sponsor
- Sir Run Run Shaw Hospital
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Organ reservation rate
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
Short-course radiotherapy combined with immunotherapy may bring revolutionary changes to the total neoadjuvant therapy mode for locally advanced ultra low rectal cancer to preserve the organs. In view of the shortcomings of the current otal neoadjuvant therapy model for locally advanced ultra low rectal cancer, we will explore the feasibility of a new model of short-course radiotherapy combined with immunotherapy, and develop a possible optimal plan based on the existing theoretical basis, namely "short-course radiotherapy + PD-L1 monoclonal antibody combined with CAPEOX chemotherapy for 8 cycles", and explore the efficacy and adverse effects of this model. The study will also attempt to explore the characteristics of the treatment beneficiary population, explore the characteristics of the treatment beneficiary population by multi-dimensional tumor and microenvironmental information through multi-omics sequencing analysis, attempt to build an efficacy prediction model, early screening of the treatment beneficiary population for precise treatment, and thus explore a new model of radiotherapy combined with immunotherapy for the poplation who can be achieved organ preservation.
Investigators
Sheng Dai
Principal Investigator, head of medical affairs
Sir Run Run Shaw Hospital
Eligibility Criteria
Inclusion Criteria
- •Patients who are willing to receive neoadjuvant therapy.
- •≧18 years old.
- •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.
- •Histologically diagnosed as rectal adenocarcinoma.
- •The clinical staging by pelvic contrast-enhanced CT and pelvic high-resolution MRI were stage I, II and III.
- •MMR protein detection or MSI gene detection of rectal cancer specimens confirmed pMMR or MSS before treatment .
- •The patient is difficult cured by anal reserve procedure based on the primary physician's practice.
- •The patient has good compliance and can come to the hospital for re-examination as required.
- •ECOG Scale of Performance Status score 0-1 point.
- •Have not received anti-tumor and immunotherapy before enrollment.
Exclusion Criteria
- •History of other malignant diseases in the past 5 years.
- •Patients with metastases from other sites (stage IV patients).
- •Patients with positive lateral lymph nodes by pelvic contrast-enhanced CT and pelvic high-resolution MRI.
- •Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. requiring emergency surgery.
- •Known allergic to oxaliplatin, capecitabine, PD-L1 monoclonal antibody and other drugs.
- •Pathologically suggested signet ring cell carcinoma and mucinous adenocarcinoma.
- •dMMR or MSI-H patients.
- •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.
- •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.
- •Active autoimmune disease that may worsen while receiving immunostimulants.
Arms & Interventions
Total Neoadjuvant Therapy with Short-course Radiation followed by Envafolimab plus CAPEOX
The enrolled patients with MSS-type advanced ultra low rectal cancer will receive a combined regimen of neoadjuvant chemoradiotherapy combined with immunotherapy and biopsy or local excision. 1. Radiotherapy uses a short-range mode, irradiating the primary tumor and high-risk areas with dose of 25 Gy. 2. After radiotherapy, PD-L1 antibody (150mg/week, subcutaneous injection × 24 weeks) immunotherapy combined with 8 courses of CAPEOX chemotherapy was performed. 3. Two weeks after the end of the combined treatment plan in step 2), biopsy or local excision of the lesion is performed.
Intervention: Envafolimab
Outcomes
Primary Outcomes
Organ reservation rate
Time Frame: After 2 weeks (once biopsy or local excision is done)
population who achieve complete clinical response after total neoadjuvant therapy
Secondary Outcomes
- Total mesorectal excision rate(After 2 weeks (once biopsy or local excision is done))
- Total mesorectal excision rate after recurrence(from primary evaluation at 2 weeks after total neoadjuvant therapy finished)
- Tumor regression grade f(After 2 weeks (once biopsy or local excision is done))
- Overall survival(Up to 3 years)
- Progression free survival(Up to 3 years)
- TRAEs(Up to 3 years)
- Surgical Complications(Up to 3 years)
- QoL(Up to 3 years)