Clinical trial NCT04443543: An Adaptive-design Prospective Cohort Study of Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Chemoradiotherapy
organ preservation
watch and wait
irinotecan
Tislelizumab
capecitabine
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-06-23
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: clinical complete response rate
timeFrame: two weeks after completion of CRT or consolidation chemotherapy.
Secondary outcomes:
measure: 2y-anal preservation rate
timeFrame: 2 years
measure: 2y-local recurrence rate
timeFrame: 2 years
measure: Impact of participants' quality of life
timeFrame: 2 years
measure: overall survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Cencer
state: Shanghai
Study officials:
References: