The Efficacy and Safety of Short-course Radiation Combined With Adebrelimab and CAPEOX Neo-adjuvant Therapy for Organ-retention in Patients With MSS/pMMR Ultra Low Rectal Adenocarcinoma

NCT06266832 | Recruiting Phase 2

• 1 other identifier: 20230727
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy, safety and organ retention rate of short-course radiation combined with Adebrelimab and CAPEOX neoadjuvant therapy in patients with MSS/pMMR ultra low rectal adenocarcinoma.

Conditions

Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Organ retention rate

  population who achieve complete clinical response after total neoadjuvant therapy

  After 2 weeks (once biopsy or local excision is done)

Secondary Outcomes (7)

• 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

  After 2 weeks (once biopsy or local excision is done)

• Overall survival

  Up to 3 years

• Disease free survival

  Up to 3 years

Study Arms (1)

Total Neoadjuvant Therapy with Short-course Radiation followed by Adebrelimab plus CAPEOX

EXPERIMENTAL

The enrolled patients with MSS-type advanced ultra low rectal adenocarcinoma will receive a combined regimen of neoadjuvant chemoradiotherapy combined with immunotherapy and biopsy or local excision. Radiotherapy uses a short-range mode, irradiating the primary tumor and high-risk areas with dose of 25 Gy. After radiotherapy, PD-L1 antibody (20mg/kg, intravenously guttae, 2courses) immunotherapy combined with 2 courses of CAPEOX chemotherapy was performed. 1-4 weeks after the end of the combined treatment plan in step 2), biopsy or local excision of the lesion is performed.

Drug: Adebrelimab; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Short-course Radiation; Procedure: Biopsy

Interventions

Adebrelimab DRUG

This product is administered by intravenously guttae. The recommended dose of subcutaneous injection is 20mg/kg, administered every 3 Weeks (Q3W).

Also known as: SHR-1316

Total Neoadjuvant Therapy with Short-course Radiation followed by Adebrelimab plus CAPEOX

Oxaliplatin DRUG

130mg/m2, ivgtt, d1, Q3W

Total Neoadjuvant Therapy with Short-course Radiation followed by Adebrelimab plus CAPEOX

Capecitabine DRUG

1000mg/m2, po, bid, d1-14, Q3W

Total Neoadjuvant Therapy with Short-course Radiation followed by Adebrelimab plus CAPEOX

Short-course Radiation RADIATION

Short-course radiotherapy, using three-dimensional conformal or intensity-modulated radiotherapy, the dose is divided into 5Gy/f, the total dose is 25Gy/5f, 1f/d, and the irradiation is completed within 7 days.

Total Neoadjuvant Therapy with Short-course Radiation followed by Adebrelimab plus CAPEOX

Biopsy PROCEDURE

local excision or TME surgery (total mesorectal excision) Biopsy can choose endoscopic or needle biopsy, colcal excision refers to excison of the local lession after total neoadjuvant therapy. The total mesorectal excision can choose open, laparoscopic or robotic according to the specific condition of the patient.

Total Neoadjuvant Therapy with Short-course Radiation followed by Adebrelimab plus CAPEOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• MMR protein detection or MSI gene detection of rectal cancer specimens confirmed pMMR or MSS before treatment .
• The clinical staging by pelvic contrast-enhanced CT and pelvic high-resolution MRI were stage I, II and III.
• 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.
• Laboratory inspections must meet the following standards:
• White blood cell count\>3.5×109/L, absolute value of neutrophils\>1.8×109/L, platelet count ≥75×109/L, hemoglobin ≥100g/L;
• 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;
• Total bilirubin ≤ 1.25 times the upper limit of normal; ALT and AST \< 5 times the upper limit of normal;
• h creatinine clearance \>50mL/min or serum creatinine \<1.5 times the upper limit of normal.
• Voluntarily participate in this study and sign the informed consent.

You may not qualify if:

• History of other malignant diseases other than rectal cancer in the past 5 years.
• Patients with metastases from other sites (stage IV patients).
• Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. requiring emergency surgery.
• Known allergic to oxaliplatin, capecitabine, Adebrelimab 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.
• Known history of positive HIV test or known acquired immunodeficiency syndrome.
• Patients who are using immunosuppressive agents, except for the following conditions:
• Intranasal, inhaled, topical steroids, or topical steroid injections (eg, intra-articular injections);
• Physiological doses of systemic corticosteroids ≤10 mg/day prednisone or equivalent; 3) Steroids used to prevent allergic reactions (eg, before CT scan).
• Received any other experimental drug treatment or participated in another interventional clinical trial within 30 days before screening.
• 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.

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead

Study Sites (1)

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Oxaliplatin; Capecitabine; Biopsy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• sheng dai, MD&PhD

  China, Zhejiang Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

sheng dai, MD&PhD

CONTACT

13575472669; daimd@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2024
• First Posted: February 20, 2024
• Study Start: January 1, 2024
• Primary Completion: January 1, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)