Locally Advanced Rectal Cancer
Conditions
Brief summary
This is an open-label, single-arm study to investigate the efficacy and safety of AK104 (an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) and neoadjuvant chemoradiotherapy in patients with pMMR/MSS locally advanced rectal cancer.
Detailed description
The study evaluates the addition of AK104(an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) in neoadjuvant chemoradiotherapy in proficient Mismatch Repair (pMMR) /Microsatellite Stable (MSS) locally advanced rectal cancer (LARC). A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage. The tumor response to treatment, adverse effects and long-term prognosis will be analyzed.
Interventions
DRUGAK104
During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.
DRUGCapecitabine
During neo-CRT: 825mg/m2 bid Monday-Friday per week
RADIATIONNeoadjuvant Radiotherapy
IMRT DT: 50Gy/25Fx
Sponsors
Akeso
Haplox Biotechnology Co., Ltd.
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 2. ECOG 0-1 3. Rectal adenocarcinoma 4. cT3-4aNany or cT1-4aN+ 5. No distant metastasis 6. Location ≤12 cm from the anal verge 7. Positive PD-L1 expression (PD-L1 TPS≥1% or PD-L1 CPS ≥1) 8. the MSI status is MSS and pMMR 9. Sufficient bone marrow, kidney and liver function 10. No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy
Exclusion criteria
1. bowel obstruction 2. Distant metastasis 3. Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV ) 4. Uncontrollable severe hypertesion 5. Active severe infection 6. Cachexia, organ dysfunction 7. Previous pelvic radiotherapy or chemotherapy 8. Multiple primary cancers 9. Epileptic seizures 10. Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma 11. Persons deprived of liberty or under guardianship 12. Impossibility for compliance to follow-up 13. Certain or suspicious allergy to research drug 14. Pregnant or breast-feeding woman
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response (CR) rate | an average of 6 months. | Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From date of randomization until the date of death from any cause, assessed up to 60 months. | 5 year overall survival rate |
| Adverse effects | From date of randomization until the date of death from any cause, assessed up to 5 years | Adverse effects according to CTCAE 5.0 |
| Rate of Major pathologic response and tumor regression grade distribution | an average of 1 year. | Rate of Major pathologic response and tumor regression grade distribution |
| Local recurrence free survival | From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. | 3 year local recurrence free survival rate |
| Disease free survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. | 3 year disease free survival rate |
| Long-term anal function | 1.5 year after diagnosis | Long-term anal function was evaluated using the Wexner Continence Grading Scale ,the score being calculated after the patients' completion of a daily defecatory questionnaire. Range is from 0 (normal continence) to 20 (maximum incontinence with maximum disturbance of lifestyle) |
| Rate of surgical complications | The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 1 year from the surgery. | Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. |
Countries
China
Contacts
Primary ContactWeiWei Xiao
Outcome results
None listed