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

NCT ID: NCT06266832

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-01
• Study Completion Date: 2027-12-31

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.

Detailed Description

At present, neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision (TME) is the main standard treatment, and the choice of treatment modalities is limited. The emergence of immunotherapy has provided a new direction for the exploration of neoadjuvant therapy for rectal adenocarcinoma. At the same time, a number of studies have also shown that appropriate radiotherapy intensity can promote immune response. Therefore, the investigators intend to conduct the clinical trail to explore the effect of short-course radiotherapy combined with PD-L1 combined and chemotherapy as TNT (total neoadjuvant therapy) on organ retention rate in patients with With MSS/pMMR Ultra Low Rectal Adenocarcinoma.

Conditions

Rectal Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Adebrelimab

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

130mg/m2, ivgtt, d1, Q3W

Capecitabine

Intervention Type: DRUG

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

Short-course Radiation

Intervention Type: 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.

Biopsy

Intervention Type: 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.

Interventions

Adebrelimab

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

Intervention Type: DRUG

Oxaliplatin

130mg/m2, ivgtt, d1, Q3W

Intervention Type: DRUG

Capecitabine

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

Intervention Type: DRUG

Short-course 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.

Intervention Type: RADIATION

Biopsy

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.

Intervention Type: PROCEDURE

Other Intervention Names

SHR-1316

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. MMR protein detection or MSI gene detection of rectal cancer specimens confirmed pMMR or MSS before treatment .

6. The clinical staging by pelvic contrast-enhanced CT and pelvic high-resolution MRI were stage I, II and III.

7. The patient has good compliance and can come to the hospital for re-examination as required.

8. ECOG Scale of Performance Status score 0-1 point.

9. Have not received anti-tumor and immunotherapy before enrollment.

10. 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.

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

Exclusion Criteria

1. History of other malignant diseases other than rectal cancer in the past 5 years.

2. Patients with metastases from other sites (stage IV patients).

3. Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. requiring emergency surgery.

4. Known allergic to oxaliplatin, capecitabine, Adebrelimab and other drugs.

5. Pathologically suggested signet ring cell carcinoma and mucinous adenocarcinoma.

6. dMMR or MSI-H patients.

7. 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.

8. 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.

9. Active autoimmune disease that may worsen while receiving immunostimulants.

10. Known history of positive HIV test or known acquired immunodeficiency syndrome.

11. 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).

12. Received any other experimental drug treatment or participated in another interventional clinical trial within 30 days before screening.

13. 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.

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sir Run Run Shaw Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

sheng dai, MD&PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

sheng dai, MD&PhD

Role: CONTACT

daimd@zju.edu.cn

13575472669

Facility Contacts

Xiujun Cai

Role: primary

Other Identifiers

20230727

Identifier Type: -

Identifier Source: org_study_id