Rectal Cancers
Conditions
Keywords
radiotherapy, immunotherapy, neoadjuvant therapy, rectal cancer
Brief summary
To explore the efficacy and safety of radiotherapy combined with Adebrelimab and NALIRIFOX in patients with pMMR/MSS locally advanced rectal cancer
Interventions
COMBINATION_PRODUCTAdalimumab+NALIRIFOX→Short course radiotherapy →Adalimumab+NALIRIFOX
Short course radiotherapy, 5 \* 5Gy, once a day, 5Gy each time, for 5 days; Adalimumab 1200 mg , D1, q2w, 2 cycles before radiotherapy and 6 cycles after radiotherapy; NALIRIFOX: Oxaliplatin 85 mg/m2, D1; Liposomal irinotecan 60 mg/m2, D1; LV 200 mg/m2; 5-FU 2400 mg/m2, Infusion for 48 hours; Repeat every 2 weeks. 2 cycles before radiotherapy and 6 cycles after radiotherapy;
COMBINATION_PRODUCTAdalimumab+NALIRIFOX→Long course chemoradiotherapy →Adalimumab+NALIRIFOX
Long course chemoradiotherapy,50 Gy in 25 fractions, during the same period, capecitabine was 825 mg / m2, twice a day, 5 days a week; Adalimumab 1200 mg , D1, q2w, 2 cycles before radiotherapy and 6 cycles after radiotherapy; NALIRIFOX: Oxaliplatin 85 mg/m2, D1; Liposomal irinotecan 60 mg/m2, D1; LV 200 mg/m2; 5-FU 2400 mg/m2, Infusion for 48 hours; Repeat every 2 weeks. 2 cycles before radiotherapy and 6 cycles after radiotherapy;
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients or their family members agree to participate in the study and sign the informed consent form; 2. Age 18-75 years, male or female; 3. Locally advanced rectal adenocarcinoma confirmed by histopathology; 4. Clinical stage cT3-4bN0M0 or cTxN+M0, with or without MRF positive, with or without EMVI positive, expected to R0 resection; 5. without intestinal obstruction; 6. ECOG PS 0-1; 7. expect survival up to 2 years; 8. White blood cell count \> 3.5×109/L；Platelet count ≥ 100×109/L；Hemoglobin ≥ 80 g/L； 9. ALT ≤ 1.5×ULN, AST ≤ 1.5×ULN ； 10. Serum creatinine ≤ 100μmol/l,
Exclusion criteria
1. With inguinal lymph node metastasis or lateral lymph node metastasis (lymph node diameter ≥7 mm, or lymph node morphology and MRI features consistent with typical metastatic lymph nodes); 2. Arrhythmia requiring antiarrhythmic treatment (except beta-blockers or digoxin), symptomatic coronary artery disease or myocardial ischemia (myocardial infarction within the last 6 months), or congestive heart failure exceeding NYHA Class II; 3. Severe hypertension poorly controlled with medication; 4. History of HIV infection, or active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL), or hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay); 5. Active pulmonary tuberculosis (TB), currently receiving anti-tuberculosis treatment, or having received anti-tuberculosis treatment within 1 year prior to screening; 6. Other active clinically severe infections (NCI-CTCAE Version 5.0); 7. Preoperative evidence of distant metastasis outside the pelvis; 8. Cachexia or organ function decompensation. 9. History of pelvic or abdominal radiotherapy; 10. Multiple primary colorectal cancers; 11. Patients with seizures requiring treatment (e.g., corticosteroids or antiepileptic therapy); 12. History of other malignancies within 5 years, except cured cervical carcinoma in situ or basal cell carcinoma of the skin; 13. Drug abuse, or medical, psychological, or social conditions that may interfere with the patient's participation in the study or affect the evaluation of study results; 14. Active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enterocolitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism); 15. Receipt of any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine, etc.) within 4 weeks prior to enrollment; 16. Comorbidities requiring long-term treatment with immunosuppressive agents, or requiring systemic or local administration of corticosteroids at immunosuppressive doses (dose \>10 mg/day of prednisone or other glucocorticoids with equivalent efficacy); 17. Known or suspected hypersensitivity to the investigational drug, or to any medication administered in relation to this study; 18. Any unstable condition that may jeopardize patient safety or compliance; 19. Pregnant or lactating women, or women of childbearing potential not using adequate contraception; 20. Refusal to sign the informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CR rate | up to 6 months | the number of patients with a pCR for those who underwent surgery and a cCR for those who underwent WW; The pCR was defined as the absence of any tumor cells from the primary tumor and lymph nodes in the specimen after radical surgery (ypT0N0) or the absence of any tumor cells in the lesion after local resection (ypT0).The cCR was defined as the absence of residual disease on DRE, MRI, and endoscopy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival(EFS) rate | an expected average of 5 years | The percentage of patients without disease recurrence or progression or death due to any cause |
| R0 resection rate | an expected average of 2 years | The rate of negative margin microscopically |
| ORR[Objective Response Rate] | an expected average of 1.5 years | Proportion of subjects in the analysis population who achieved complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. |
| OPR | an expected average of 1.5 years | Organ Preservation Rate |
| Overall Survival | an expected average of 5 years | The time from the date of randomization to the death caused by any cause |
| Adverse events (AEs) | an expected average of 1.5 years | Adverse events and surgical safety |
Countries
China
Contacts
CONTACTChi Zhou
Outcome results
None listed