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

NCT04443543 | Not Yet Recruiting Phase 2

• 1 other identifier: CARTOnG-2001
• Study Type: interventional
• Target: 222
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 2y-anal preservation rate

  2 years

• 2y-local recurrence rate

  2 years

• Impact of participants' quality of life

  2 years

• overall survival

  3 years

Study Arms (2)

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.

Drug: Capecitabine (Xeloda) Pharmacogenetic Test Reagents; Drug: irinotecan; Radiation: IMRT; Drug: Oxaliplatin; Drug: 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.

Drug: Capecitabine (Xeloda) Pharmacogenetic Test Reagents; Drug: irinotecan; Radiation: IMRT; Drug: Tislelizumab

Interventions

Capecitabine (Xeloda) Pharmacogenetic Test Reagents DRUG

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

Arm 1; Arm 2

irinotecan DRUG

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

Arm 1; Arm 2

IMRT RADIATION

Pelvic Radiation: 50Gy/25Fx

Arm 1; Arm 2

Oxaliplatin DRUG

FOLFIRINOX: 85mg/m2 d1

Arm 1

5Fluorouracil DRUG

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

Arm 1

Tislelizumab DRUG

200mg iv

Arm 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Cencer

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine; Irinotecan; Oxaliplatin; Fluorouracil; tislelizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

Central Study Contacts

Ji Zhu

CONTACT

+86-2164175590; leo.zhu@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principle investigator

Study Record Dates

• First Submitted: June 20, 2020
• First Posted: June 23, 2020
• Study Start: June 22, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 30, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)