An Adaptive-design Prospective Cohort Study of Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer
- Conditions
- Rectal Cancer
- Interventions
- Registration Number
- NCT04443543
- Lead Sponsor
- Fudan University
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 222
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 IMRT 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 1 5Fluorouracil 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 Capecitabine (Xeloda) Pharmacogenetic Test Reagents 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. Arm 2 IMRT 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. Arm 1 Capecitabine (Xeloda) Pharmacogenetic Test Reagents 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 1 irinotecan 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 1 Oxaliplatin 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 irinotecan 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. Arm 2 Tislelizumab 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (1)
Fudan University Shanghai Cancer Cencer
🇨🇳Shanghai, Shanghai, China