Rectal Cancer
Conditions
Keywords
Chemoradiotherapy, organ preservation, watch and wait, irinotecan, Tislelizumab, capecitabine
Brief summary
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.
Detailed description
1. 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) 2. 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. 3. 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.
Interventions
DRUGCapecitabine (Xeloda) Pharmacogenetic Test Reagents
CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14
DRUGirinotecan
CRT:80mg/m2 (UGT1A1\*28 6/6) or 65mg/m2 (UGT1A1\*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1
RADIATIONIMRT
Pelvic Radiation: 50Gy/25Fx
DRUGOxaliplatin
FOLFIRINOX: 85mg/m2 d1
DRUG5Fluorouracil
FOLFIRINOX: 400mg/m2 iv d1bolus, 2400mg/m2 ivgtt 46h
DRUGTislelizumab
200mg iv
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* pathological confirmed adenocarcinoma * clinical stage T2-4 and/or N+, inappropriate for local excision * the distance from anal verge less than 5 cm, or considered inappropriate for anal preservation by surgeons. * Strong desire to preserve the anus, able to receive close surveillance for at least 2 years after chemoradiotherapy. * without distance metastases * aged between 18 to 75 years old. * performance status score: 0\ 1 * UGT1A1\*28 6/6 or 6/7 * sign the inform consent
Exclusion criteria
* pregnancy or breast-feeding women * serious medical illness * difficult to achieve complete response assessed by current evidence: the maximal diameter of tumor \>10cm; the maximal diameter of lateral lymph node \>2cm; baseline CEA\>=100; biopsy pathology confirmed signet ring cell carcinoma components; digital rectal examination found that the tumor is peri-narrowed. * baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10\^9/L, Hb≥90g/L, PLT≥100×10\^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN * DPD deficiency * UGT1A1\*28 7/7
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| clinical complete response rate | two weeks after completion of CRT or consolidation chemotherapy. | After nCRT, the lesions of rectal completely respond. Tumor residue cannot be found by digital rectal examination, endoscopic biopsy and radiology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2y-anal preservation rate | 2 years | 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. |
| 2y-local recurrence rate | 2 years | 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. |
| Impact of participants' quality of life | 2 years | quality of life is evaluated according to EORTC C-30 questionnare. |
| overall survival | 3 years | 3-year OS will be defined as the percentage of patients alive at 3 years measured from the date of completion of CRT. |
Countries
China
Contacts
Primary ContactJi Zhu
Outcome results
None listed