Clinical trial NCT06266832: 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
Official title: 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: A Prospective, Single-arm Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Adenocarcinoma
Lead sponsor: Sir Run Run Shaw Hospital
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Organ retention rate
timeFrame: After 2 weeks (once biopsy or local excision is done)
Secondary outcomes:
measure: Total mesorectal excision rate
timeFrame: After 2 weeks (once biopsy or local excision is done)
measure: Total mesorectal excision rate after recurrence
timeFrame: from primary evaluation at 2 weeks after total neoadjuvant therapy finished
measure: Tumor regression grade
timeFrame: After 2 weeks (once biopsy or local excision is done)
measure: Overall survival
timeFrame: Up to 3 years
measure: Disease free survival
timeFrame: Up to 3 years
measure: TRAEs
timeFrame: Up to 3 years
measure: QoL
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: China, Zhejiang Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
name: sheng dai, MD&PhD
role: PRINCIPAL_INVESTIGATOR
References: