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

NCT ID: NCT04443543

Last Updated: 2020-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

222 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-22

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Rectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

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.

Group Type EXPERIMENTAL

Capecitabine (Xeloda) Pharmacogenetic Test Reagents

Intervention Type DRUG

CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14

irinotecan

Intervention Type DRUG

CRT:80mg/m2 (UGT1A1\*28 6/6) or 65mg/m2 (UGT1A1\*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1

IMRT

Intervention Type RADIATION

Pelvic Radiation: 50Gy/25Fx

Oxaliplatin

Intervention Type DRUG

FOLFIRINOX: 85mg/m2 d1

5Fluorouracil

Intervention Type DRUG

FOLFIRINOX: 400mg/m2 iv d1bolus, 2400mg/m2 ivgtt 46h

Arm 2

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.

Group Type EXPERIMENTAL

Capecitabine (Xeloda) Pharmacogenetic Test Reagents

Intervention Type DRUG

CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14

irinotecan

Intervention Type DRUG

CRT:80mg/m2 (UGT1A1\*28 6/6) or 65mg/m2 (UGT1A1\*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1

IMRT

Intervention Type RADIATION

Pelvic Radiation: 50Gy/25Fx

Tislelizumab

Intervention Type DRUG

200mg iv

Interventions

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Capecitabine (Xeloda) Pharmacogenetic Test Reagents

CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14

Intervention Type DRUG

irinotecan

CRT:80mg/m2 (UGT1A1\*28 6/6) or 65mg/m2 (UGT1A1\*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1

Intervention Type DRUG

IMRT

Pelvic Radiation: 50Gy/25Fx

Intervention Type RADIATION

Oxaliplatin

FOLFIRINOX: 85mg/m2 d1

Intervention Type DRUG

5Fluorouracil

FOLFIRINOX: 400mg/m2 iv d1bolus, 2400mg/m2 ivgtt 46h

Intervention Type DRUG

Tislelizumab

200mg iv

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fudan University

OTHER

Sponsor Role lead

Responsible Party

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Zhu Ji

principle investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Fudan University Shanghai Cancer Cencer

Shanghai, Shanghai Municipality, China

Site Status

Countries

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China

Central Contacts

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Ji Zhu

Role: CONTACT

+86-2164175590 ext. 81607

Other Identifiers

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CARTOnG-2001

Identifier Type: -

Identifier Source: org_study_id

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