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This is a multicenter, cohort, prospective study to evaluate the efficacy and safety of Adebrelimab combined with radiotherapy and chemotherapy as preoperative neoadjuvant therapy for patients with locally advanced rectal cancer. In the study, all subjects who meet the inclusion criteria will enter the short-term radiotherapy queue and the long-term radiotherapy queue at the ratio of 1:1. The short-term radiotherapy queue plans to receive Adebrelimab combined with short-term radiotherapy (5*5Gy) and Capox chemotherapy as neoadjuvant therapy. The long-term radiotherapy queue plans to receive Adebrelimab combined with long-term radiotherapy (1.8gy × 25-28 times) and capox chemotherapy as neoadjuvant therapy. The TME surgery will be performed 2-3 weeks after the last neoadjuvant therapy is completed. If the surgery cannot be performed within the time window specified in the plan (such as delayed adverse reactions, etc.), the researcher will conduct the surgery according to the patients' requirements.The actual clinical conditions of the subjects were comprehensively considered.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | Radiotherapy protocol: 5 × 5Gy short-term radiotherapy (D1-5 in the first week) Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ~ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme. |
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| Group 2 | Experimental | Radiotherapy regimen: long-term radiotherapy 1.8 × 25-28Gy, oral capecitabine in the same period: the standard dose is 825mg/m2, twice a day [total dose 1650mg/(M2 · d)], oral radiotherapy day, 5 days a week. Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ~ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| short-term radiotherapy combined with Adebrelimab and capox | Combination Product | Radiotherapy protocol: 5 × 5Gy short-term radiotherapy (D1-5 in the first week) Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ~ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme. |
| Measure | Description | Time Frame |
|---|---|---|
| CR rate | pathological complete remission rate (PCR) and clinical complete remission rate (CCR) | From enrollment to the end of surgery,assessed up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| partial remission rate (PR) | the total diameter of all measurable target lesions is ≥ 30% lower than the baseline | The evaluation time from enrollment to the first efficacy evaluation is up to 3 months |
| Objective response rate (ORR) |
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Inclusion Criteria:
1. sign written informed consent before implementing any test related process;
2. Patients diagnosed as rectal adenocarcinoma by primary biopsy and histopathological examination;
3. patients with CT stage ≥ T3 or CN stage N1+, M0 or EMVI (+) or MRF (+) or suspected lateral lymph node metastasis (>5mm) who are judged by imaging and colonoscopy to be operable and need neoadjuvant therapy.
4. according to imaging and colonoscopy, the main body of the tumor was located ≤ 10cm from the anal edge;
5. patients with tumor mismatch repair/microsatellite instability (MMR/MSI) status as MSS;
6. according to the criteria for evaluating the efficacy of solid tumors (RECIST version 1.1), at least one lesion can be measured by imaging;
7. the patient has not received any anti-tumor treatment in the past, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy, etc;
8. ECoG score: 0-1;
9. sufficient organ function, the subject shall meet the following laboratory indicators:
10. female subjects of childbearing age should receive urine or serum pregnancy test within 3 days before receiving the first study drug administration (the first day of the first cycle) and the result is negative. If the result of urine pregnancy test cannot be confirmed as negative, blood pregnancy test is required. Women of non reproductive age were defined as having been postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy; If there is a risk of pregnancy, all subjects (male or female) need to take contraceptive measures with an annual failure rate of less than 1% during the whole treatment period until 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).
Exclusion Criteria:
Note: hepatitis B subjects who meet the following criteria can also be enrolled:
HBV viral load<1000 copies/ml (200 iu/ml) before the first administration. Subjects should receive anti HBV treatment during the whole study chemotherapy drug treatment to avoid virus reactivation
For subjects with anti HBC (+), HBsAg (-), anti HBS (-) and HBV viral load (-), preventive anti HBV treatment is not required, but virus reactivation needs to be closely monitored
1) The resting ECG has significant abnormalities in rhythm, conduction or morphology, and the symptoms are serious and difficult to control, such as complete left bundle branch block, heart block above grade II, ventricular arrhythmia or atrial fibrillation; 2) Unstable angina pectoris, congestive heart failure, chronic heart failure with NYHA classification ≥ 2; 3) Myocardial infarction occurred within 6 months before enrollment; 4) Blood pressure control was not ideal (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg); 5) There was a history of non infectious pneumonia requiring glucocorticoid treatment within 1 year before the first administration, or there was currently clinically active interstitial lung disease; 6) Active pulmonary tuberculosis; 7) Active or uncontrolled infection requiring systemic treatment; 8) There were clinically active diverticulitis, abdominal abscess and gastrointestinal obstruction; 9) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; 10) Poor control of diabetes mellitus (FBG>10mmol/L); 11) The urine routine showed that the urine protein was ≥++, and it was confirmed that the 24-hour urine protein quantitation was more than 1.0 G; 12) Patients with mental disorders and unable to cooperate with treatment;
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Feng Tian, Dr. | Contact | +86 18866102886 | tianfeng@sdu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Changqing Jing, Professor | Shandong Provincial Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shandong Provincial Hospital Affiliated to Shandong First Medical University | Recruiting | Jinan | Shandong | 250021 | China |
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| long-term radiotherapy combined with Adebrelimab and capox | Combination Product | Radiotherapy regimen: long-term radiotherapy 1.8 × 25-28Gy, oral capecitabine in the same period: the standard dose is 825mg/m2, twice a day [total dose 1650mg/(M2 · d)], oral radiotherapy day, 5 days a week. Immunotherapy regimen: Adebrelimab 1200 mg or 20 mg/kg, IV., administered on the first day of each chemotherapy cycle. Chemotherapy regimen: capox regimen: Oxaliplatin 130 mg/m2 IV D1 Capecitabine 1000 mg/m2 Po bid D1 ~ 14 Repeat every 3 weeks for 6 cycles The curative effect was evaluated 2-3 weeks after the completion of 6 cycles of chemotherapy. According to whether the CCR (clinical complete remission) was achieved, TME surgery was required if the CCR was not achieved; If CCR is achieved, TME operation can be performed according to the wishes of the patients. Local resection or observation through anal surgery requires close follow-up to explore the effectiveness and safety of the scheme. |
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Proportion of subjects defined as complete remission (CR) and partial remission (PR) in total subjects
| The evaluation time from enrollment to the first efficacy evaluation is up to 3 months |
| Major Pathological Response Rate (MPR) | Major Pathological Response Rate (MPR) | From enrollment to the end of surgery,assessed up to 6 months |
| R0 resection rate | There is no visible tumor residue in the body, and no residual tumor cells are found under the pathological microscope | From enrollment to the end of surgery,assessed up to 6 months |
| 2-year DFS rate | 2-year progression free survival rate | The longest follow-up time was 2 years from enrollment to disease progression |
| 3-year OS rate | 3-year OS rate | The longest follow-up time was 3 years from enrollment to death from any cause |
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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