An Adaptive-design Prospective Cohort Study of Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer

Rectal Cancer Clinical Trial

Official title:

Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy: A Multi-centre, Adaptive-design, Phase II Prospective Cohort Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04443543
• Other study ID #: CARTOnG-2001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 22, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2020
• Source: Fudan University
• Contact: Ji Zhu
• Phone: +86-2164175590
• Email: leo.zhu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 222
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Capecitabine (Xeloda) Pharmacogenetic Test Reagents
CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14
• irinotecan
CRT:80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1

Radiation:
• IMRT
Pelvic Radiation: 50Gy/25Fx

Drug:
• Oxaliplatin
FOLFIRINOX: 85mg/m2 d1
• 5Fluorouracil
FOLFIRINOX: 400mg/m2 iv d1bolus, 2400mg/m2 ivgtt 46h
• Tislelizumab
200mg iv

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Cencer	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Secondary	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
Secondary	2y-local recurrence rate	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
Secondary	Impact of participants' quality of life	quality of life is evaluated according to EORTC C-30 questionnare.	2 years
Secondary	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