Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
CARTOnG-2001
- NCT ID:
NCT04443543
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Capecitabine (Xeloda) Pharmacogenetic Test Reagents | | Arm 1 |
| irinotecan | | Arm 1 |
| Oxaliplatin | | Arm 1 |
| 5Fluorouracil | | Arm 1 |
| Tislelizumab | | Arm 2 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - Capecitabine (Xeloda) Pharmacogenetic Test Reagents
- irinotecan
- Oxaliplatin
- 5Fluorouracil
|
| 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. | - Capecitabine (Xeloda) Pharmacogenetic Test Reagents
- irinotecan
- Tislelizumab
|
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
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | clinical complete response rate |
| Time Frame: | two weeks after completion of CRT or consolidation chemotherapy. |
| Safety Issue: | |
| Description: | After nCRT, the lesions of rectal completely respond. Tumor residue cannot be found by digital rectal examination, endoscopic biopsy and radiology. |
Secondary Outcome Measures
| Measure: | 2y-anal preservation rate |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 2y-local recurrence rate |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Impact of participants' quality of life |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | quality of life is evaluated according to EORTC C-30 questionnare. |
| Measure: | overall survival |
| Time Frame: | 3 years |
| Safety Issue: | |
| Description: | 3-year OS will be defined as the percentage of patients alive at 3 years measured from the date of completion of CRT. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Fudan University |
Trial Keywords
- Chemoradiotherapy
- organ preservation
- watch and wait
- irinotecan
- Tislelizumab
- capecitabine
Last Updated
June 30, 2020
