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This phase II/III trial studies how well neoadjuvant short-course radiotherapy and chemotherapy with or without PD-1 inhibitors works in treating patients with locally advanced rectal adenocarcinoma. Neoadjuvant short-course radiation therapy followed by two-drug regimen chemotherapy, such as CAPOX, were shown to be non-inferior to standard long-course chemoradiotherapy in our previous STELLAR study. Immune checkpoint inhibitors (ICIs) using monoclonal antibodies, such as PD-1 or PD-L1 inhibitor, show promising efficiency and reliable security in some limited sample prospective or retrospective studies. When treating patients with locally advanced rectal cancer, giving sequential neoadjuvant short-course radiotherapy and chemotherapy with PD-1 inhibitor may work better.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| iTNT group | Experimental | The intervention of iTNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy and PD-1 inhibitor, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of PD-1 inhibitor and four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of PD-1 inhibitor and CAPOX treatment includes Sintilimab 200 mg IV, day 1,Oxaliplatin 130 mg/m2 IV day 1,Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of PD-1 inhibitor and mFOLFOX treatment includes Sintilimab 200 mg IV day 1(3 weeks per cycle), Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch & Wait strategy for clinical complete remission voluntary patients. |
|
| TNT group | Active Comparator | The intervention of TNT group is Short-course radiotherapy followed by neoadjuvant chemotherapy, which consists of a short-course radiotherapy(SCRT, 5 Gy x 5 alone), then after 14 days of radiotherapy completed, four cycles of CAPOX or six cycles of mFOLFOX will be performed. The regimen of CAPOX treatment includes Oxaliplatin 130 mg/m2 IV day 1,Capecitabine 1000 mg/m2 twice daily PO for 14 days(3 weeks per cycle). The regimen of mFOLFOX treatment includes, Oxaliplatin 85 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion(2 weeks per cycle), then followed by a total mesorectal excision(TME) or Watch & Wait strategy for clinical complete remission voluntary patients. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sintilimab | Drug | PD-1 inhibitor |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| complete remission | The rate of pathological complete remission plus clinical complete remission | one year |
| Disease-free survival rate | three year |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of acute toxicities during radiation, chemotherapy ± immunotherapy | three months | |
| Incidence of surgical complications | 30 days | |
| Overall survival rate |
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Inclusion Criteria:
Biopsy proven rectal adenocarcinoma;
Distance between tumour and anal verge≤ 10cm;
Locally advanced tumour;(8th edition AJCC/UICC staging :cT3-T4N0/cT2-4N+,M0) Cancer Staging must be based on pelvic MRI or Endoscopic ultrasound;
Eastern Cooperative Oncology Group(ECOG) performance score ≤ 1;
Mentally and physically fit for chemotherapy; Adequate blood counts: White blood cell count ≥3.5 x 109/L Haemoglobin levels ≥100g/L Platelet count ≥100 x 109/L Creatinine levels ≤1.0× upper normal limit(UNL) Urea nitrogen levels ≤1.0× upper normal limit(UNL) Alanine aminotransferase(ALT) ≤1.5× upper normal limit(UNL) Aspartate aminotransferase(AST) ≤1.5× upper normal limit(UNL) Alkaline phosphatase(ALP) ≤1.5× upper normal limit(UNL) Total bilirubin(TBIL)
≤1.5× upper normal limit(UNL)
No excision of tumor, chemotherapy or other anti-tumor treatment after the diagnosis.
No previous pelvic radiation history;
Written informed consent;
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yuan Tang | Contact | +86-15011304945 | tangyuan82@126.com | |
| Wenjue Zhang | Contact | +86-13620986880 | wenjuezhang@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College | Beijing | Beijing Municipality | China | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40845854 | Derived | Tang Y, Li HY, Wei LC, Li N, Zhang WJ, Lu YF, Deng FY, Xu TZ, Shuai JC, Lei ZF, Meng XY, Qi SN, Song YW, Zhang WW, Jing H, Li G, Liu SX, Wang YJ, Liu Z, Ma HY, Wang NY, Chen B, Wang SL, Li YX, Zhao LN, Tang JQ, Jiang Z, Chen YG, Zhou HT, Hu C, Jin J. Short-course-based TNT with or without PD-1 inhibitor for pMMR locally advanced rectal cancer: Phase 2 results of a randomized trial (STELLAR II). Med. 2025 Nov 14;6(11):100807. doi: 10.1016/j.medj.2025.100807. Epub 2025 Aug 21. | |
| 39020518 |
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| Short-course radiotherapy | Radiation | Pelvic radiation |
|
|
| CAPOX/mFOLFOX | Combination Product | chemotherapy regimen |
|
|
| three year |
| Locoregional recurrence rate | three year |
| Distance metastasis rate | three year |
| Radical resection (R0) | one year |
| Quality of life (QoL) | Quality of life will be evaluated using EORTC QLQ-C30 (range 0-100). It evaluates the quality of life from 30 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life. | From date of randomization until the date of death from any cause, assessed up to 10 years |
| Quality of life (QoL) | Quality of life will be evaluated using EORTC QLQ-Cr29 (range 0-100). It evaluates the quality of life from 29 aspects, including defecation function, urine function,pain, sex function, etc. The higher scores mean a better quality of life. | From date of randomization until the date of death from any cause, assessed up to 10 years |
| Quality of life (QoL) | Quality of life will be evaluated using Wexner score(range 0-20). It evaluates the defecation function. The lower scores mean a better quality of life. | From date of randomization until the date of death from any cause, assessed up to 10 years |
| National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College |
| Shenzhen |
| China |
| Derived |
| Zhang W, Tang Y, Wei L, Liu S, Wang W, Chi Y, Wang Y, Kang W, Huang W, Deng F, Li H, Ma H, Jiang L, Ding Z, Feng L, Li Y, Chen Y, Zhou H, Hu C, Jin J. Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II/III trial (STELLAR II study). Colorectal Dis. 2024 Sep;26(9):1732-1740. doi: 10.1111/codi.17090. Epub 2024 Jul 17. |
| 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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| ID | Term |
|---|---|
| C000632826 | sintilimab |
| D000082082 | Immune Checkpoint Inhibitors |
| D020360 | Neoadjuvant Therapy |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
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