Rectal Adenocarcinoma
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of short-course radiotherapy followed by ivonescimab and chemotherapy in participants with pMMR/MSS locally advanced rectal cancer. Patients were randomly assigned to experimental group A or control group B according to a 1:1 ratio. In group A, patients will receive neoadjuvant short-course radiotherapy followed by ivonescimab and chemotherapy. In group B, patients will receive neoadjuvant short-course radiotherapy followed by chemotherapy. After neoadjuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator, (2) Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy).
Interventions
DRUGlvonescimab
lvonescimab, DS1, D1,q3w, intravenous infusion
Oxaliplatin 130 mg / m2, D1, intravenous infusion, q3w, Capecitabine 1000 mg / m2,twice a day, oral,1-14 days, then rest for 7 days, q3w.
RADIATIONradiotherapy
5\* 5Gy, once a day, 5Gy each time, for 5 days
PROCEDURESurgery or watch&wait
The surgical method is selected by the investigator. Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy)
Sponsors
Akeso
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. Age between 18 and 75 years; 2. ECOG perfommance status of 0 or 1; 3. Life expectancy: more than 2 years; 4. Histologically proven rectal adenocarcinoma; 5. Tumor biopsy immunohistochemistry proven pMMR, positive for four proteins, MLH1, MSH2, MSH6 and PMS2, or MSS determined by gene testing; 6. According to the 8th Edition of the AJCC Staging Manual, clinical stage cT3-4NanyM0 or cTxN+M0 of II-III rectal cancer was determined by Magnetic resonance imaging (MRI)±transrectal ultrasonography/ ultrasound endoscopy. Lower edge of the tumor was ≤ 12 cm from the anal verge; 7. Eligible for R0 surgery; 8. No prior anti-tumor treatment for rectal cancer,including radiotherapy,chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc; 9. Adequate organ function; 10. Males or females with reproductive ability who are willing to use contraception in the trial;
Exclusion criteria
1. Any distant metastasis or inoperable disease, regardless clinical stage; 2. Previous (within 5 years) or concurrent other malignant tumors, excluding those that have been cured; 3. Current presence of gastric intestine obstruction, bleeding or perforation which need emergency surgery; 4. Multiple primary rectal cancers; 5. Previous pelvic or abdominal radiotherapy; 6. Difficulty swallowing; 7. Current presence of uncontrolled combined disease; 8. Active clinical infections; 9. History of severe bleeding tendency or coagulation dysfunction; 10. Presence or history of immunodeficiency; positive for HIV antibodies, current long-term use of systemic corticosteroids or other immunosuppressants; 11. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection; 12. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study; 13. Local or systemic disease caused by non-malignancy, or disease or symptom secondary to tumor, that can lead to higher medical risk and/or uncertainty in survival;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Through study completion, an average of 6 month | Adverse events and surgical safety |
| Complete response rate | 4 weeks after curative surgery for pCR; 2-4 weeks after the completion of neoadjuvant therapy (last dose of capecitabine) for cCR | The proportion of CR cases (pCR for those who underwent surgery and cCR for those who didn't receive surgery) |
| Clinical complete response rate | 2-4 weeks after the completion of neoadjuvant therapy (last dose of capecitabine) | The proportion of clinical complete response cases. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local recurrence | 3 years after Randomization | Local recurrence |
| Distant metastasis | 3 years after Randomization | Distant metastasis |
| Pathologic complete response | 4 weeks after surgery | The proportion of pathologic complete response cases for those who underwent surgery |
| EFS | 3 years after Randomization | Event free of survival |
| OS | 3 years after Randomization | Overall survial |
| TRG | 4 weeks after surgery | Tumor regression grade according to AJCC TRG grading system |
| R0 resection rate | 4 weeks after surgery | R0 resection rate |
Outcome results
None listed