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

Primary Purpose

Rectal Cancer

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Capecitabine (Xeloda) Pharmacogenetic Test Reagents

irinotecan

IMRT

Oxaliplatin

5Fluorouracil

Tislelizumab

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Chemoradiotherapy, organ preservation, watch and wait, irinotecan, Tislelizumab, capecitabine

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fudan University Shanghai Cancer Cencer

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

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 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Impact of participants' quality of life

quality of life is evaluated according to EORTC C-30 questionnare.

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.

Full Information

NCT ID

NCT04443543

First Posted

June 20, 2020

Last Updated

June 27, 2020

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT04443543

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

June 22, 2020 (Anticipated)

Primary Completion Date

June 30, 2026 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

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) 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Cancer

Keywords

Chemoradiotherapy, organ preservation, watch and wait, irinotecan, Tislelizumab, capecitabine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

222 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

Arm Title

Arm 2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Capecitabine (Xeloda) Pharmacogenetic Test Reagents

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

irinotecan

Intervention Description

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

Radiation

Intervention Name(s)

IMRT

Intervention Description

Pelvic Radiation: 50Gy/25Fx

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Intervention Description

FOLFIRINOX: 85mg/m2 d1

Intervention Type

Drug

Intervention Name(s)

5Fluorouracil

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Tislelizumab

Intervention Description

200mg iv

Primary Outcome Measure Information:

Title

clinical complete response rate

Description

After nCRT, the lesions of rectal completely respond. Tumor residue cannot be found by digital rectal examination, endoscopic biopsy and radiology.

Time Frame

two weeks after completion of CRT or consolidation chemotherapy.

Secondary Outcome Measure Information:

Title

2y-anal preservation rate

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.

Time Frame

2 years

Title

2y-local recurrence rate

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.

Time Frame

2 years

Title

Impact of participants' quality of life

Description

quality of life is evaluated according to EORTC C-30 questionnare.

Time Frame

2 years

Title

overall survival

Description

3-year OS will be defined as the percentage of patients alive at 3 years measured from the date of completion of CRT.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ji Zhu

Phone

+86-2164175590

Ext

81607

leo.zhu@126.com

Facility Information:

Facility Name

Fudan University Shanghai Cancer Cencer

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

12. IPD Sharing Statement

Plan to Share IPD

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

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