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The study is designed to test the hypothesis that the clinical complete response (CCR) rate of patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy will increase after an adaptive-design paradigm, as well as the rate of 2-year organ preservation, recurrence, quality of life, DFS and OS.
Primary objective:
Evaluate the CCR rate of low rectal cancer using adaptive and optimized chemotherapy and radiotherapy strategies (all population and dMMR/MSI-H subgroup)
Secondary objectives:
2.1 Evaluate the 2-year anal preservation rate, recurrence rate, quality of life, DFS and OS 2.2 Explore the subgroup of patients suitable for observation.
Outline:
Patients after long-course chemoradiation are grouped based on their MSI-H/dMMR status. For patients with MSI-H/dMMR, consolidation immunotherapy of Tislelizumab (BGB-A317) will be assigned. For patients with MSS/pMMR, consolidation chemotherapy will be given according to their tumor response. After completion of consolidation therapy, those who reach clinical complete response will receive organ preservation (watch and wait) strategy in place of radical surgery. During treatment, once local regrowth occurs or poor tumor response, total mesorectal excision (TME) surgery will be performed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Arm 1 includes patients with MSS/pMMR. In this arm, patients receive consolidation chemotherapy after neoadjuvant chemoradiation (nCRT). The chemotherapy regimens either XELIRI or FOLFIRINOX, and the cycles of chemotherapy depend on patient tumor responses. For patients who reach cCR will enter the "W&W" cohort and omit radical surgery, while those without cCR will receive radical surgery. |
|
| Arm 2 | Experimental | Arm 2 includes patients with MSI-H/dMMR status. In this arm, patients receive consolidation immunotherapy of 3 cycles of tislelizumab after nCRT. For patients who reach cCR will enter the "W&W" cohort and omit radical surgery, while those without cCR will receive radical surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capecitabine (Xeloda) Pharmacogenetic Test Reagents | Drug | CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14 |
|
| Measure | Description | Time Frame |
|---|---|---|
| clinical complete response rate | After nCRT, the lesions of rectal completely respond. Tumor residue cannot be found by digital rectal examination, endoscopic biopsy and radiology. | two weeks after completion of CRT or consolidation chemotherapy. |
| Measure | Description | Time Frame |
|---|---|---|
| 2y-anal preservation rate | 2-year anal preservation rate will be defined as the percentage of patients alive without receiving abdominoperineal resection at 2 years measured from the date of completion of CRT. | 2 years |
| 2y-local recurrence rate |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ji Zhu | Contact | +86-2164175590 | 81607 | leo.zhu@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Cencer | Shanghai | Shanghai Municipality | 200032 | China |
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| irinotecan | Drug | CRT:80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1 |
|
| IMRT | Radiation | Pelvic Radiation: 50Gy/25Fx |
|
| Oxaliplatin | Drug | FOLFIRINOX: 85mg/m2 d1 |
|
| 5Fluorouracil | Drug | FOLFIRINOX: 400mg/m2 iv d1bolus, 2400mg/m2 ivgtt 46h |
|
| Tislelizumab | Drug | 200mg iv |
|
2-year local recurrence rate will be defined as the percentage of patients alive developing local recurrence at 2 years measured from the date of completion of CRT.
| 2 years |
| Impact of participants' quality of life | quality of life is evaluated according to EORTC C-30 questionnare. | 2 years |
| overall survival | 3-year OS will be defined as the percentage of patients alive at 3 years measured from the date of completion of CRT. | 3 years |
| 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 |
|---|---|
| D000069287 | Capecitabine |
| D000077146 | Irinotecan |
| D000077150 | Oxaliplatin |
| D005472 | Fluorouracil |
| C000707970 | tislelizumab |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
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