Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102 (Neo-REACT): A Multi-center, Randomized, Phase III Trial

NCT06850090 | Recruiting Phase 3

• 1 other identifier: SDZLEC2025-026-02
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant fluoropyrimidine-based chemoradiotherapy followed by total mesorectal excision (TME) is the standard of care for locally advanced rectal cancer (LARC); however, pathologic complete response (pCR) rates are low. Trifluridine/tipiracil (TAS-102) is a new oral anti-tumor oral formulation of nucleoside analogue, trifluridine (FTD), and a thymidine phosphorylase inhibitor, tipiracil (TPI). Previous studies have shown that TAS-102 has shown clinically relevant activity after fluoropyrimidine failure in colorectal cancer and may thus be of increased efficacy compared with current standard capecitabine chemoradiation. Also, a phase 2 trials conducted by our team have demonstrated that neoaduvant TAS-102 concurrent with long-course radiotherapy could lead to a high pCR rate of 32% with acceptable toxicity for LARC patients. Herein, we will conduct this multicenter, randomized controlled, phase III trial to explore the safety and efficacy benefit of TAS-102 concurrent with long-course radiotherapy for LARC.

Conditions

Rectal Cancer Patients; Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Complete response (CR) rate

  The primary outcomes is CR rate, which is the sum of the number of patients with a pCR who undergo surgery plus the number of patients with a cCR who undergo watch-and-wait divided by the total number of evaluable patients.

  1 year

Secondary Outcomes (3)

• The incidence of 3-4 grade adverse reactions

  1 year

• 3-year recurrence-free survival (RFS)

  3 year

• 3-year overall survival (OS)

  3 year

Study Arms (2)

TAS-102 group

EXPERIMENTAL

Neoadjuvant long-course radiotherapy combined with TAS-102

Combination Product: TAS-102

Capecitabine group

ACTIVE COMPARATOR

Neoadjuvant long-course radiotherapy combined with capecitabine

Combination Product: Capecitabine

Interventions

TAS-102 COMBINATION_PRODUCT

Radiotherapy: 1. Radiotherapy Technique: Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), or volume modulated arc therapy (VMAT); 2. Radiotherapy Dose and Fractionation Schedule: Conventional fractionation with external beam irradiation at a dose of 50 Gy delivered in 25 fractions over 5 weeks. Synchronous Chemotherapy: Concurrent administration of TAS-102 at a dose of 35 mg/m² twice daily at the 1st, 3rd and 5th week of radiotherapy. Intermittent Consolidation Chemotherapy: Oxaliplatin at 85 mg/m² on day 1 combined with TAS-102 at 35 mg/m² twice daily from day 1 to day 5, repeated every 14 days for a total of 6 cycles. Surgery: The operation follows the principle of TME. The type of surgery depends on the location and extent of the primary tumor. Postoperative adjuvant therapy: Two cycles of CapeOX (Oxaliplatin 130 mg/m2 on day 1+ capecitabine 1000 mg/m2 twice a day on days 1-14, q3w).

TAS-102 group

Capecitabine COMBINATION_PRODUCT

Radiotherapy: 1. Radiotherapy Technique: Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), or volume modulated arc therapy (VMAT); 2. Radiotherapy Dose and Fractionation Schedule: Conventional fractionation with external beam irradiation at a dose of 50 Gy delivered in 25 fractions over 5 weeks. Synchronous Chemotherapy: Capecitabine administered orally at a dose of 825 mg/m² twice daily on days of radiotherapy. Intermittent Consolidation Chemotherapy: Oxaliplatin at 130 mg/m² on day 1 combined with capecitabine at 1000 mg/m² twice daily from day 1 to day 14, repeated every 21 days for a total of 4 cycles. Surgery: The operation follows the principle of TME. The type of surgery depends on the location and extent of the primary tumor. Postoperative adjuvant therapy: Two cycles of CapeOX (Oxaliplatin 130 mg/m2 on day 1+ capecitabine 1000 mg/m2 twice a day on days 1-14, q3w)

Capecitabine group

Eligibility Criteria

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

You may qualify if:

• Patients aged between 18 and 75 years of either sex.
• Histologically confirmed rectal adenocarcinoma with the following conditions:
• Clinical stage II (T3-4, N-) or III (any T, N+) as determined by MRI.
• The tumor is located within 12 cm from the anal margin, with at least one high-risk factors (ie, extramural vascular invasion \[EMVI+\], mesorectal fascia involved \[MRF+\], cT4, cN2, lateral lymph nodes, tumor deposit, or tumor located in the lower rectum \[≤5 cm from the anal verge\]).
• No other types of rectal cancer (e.g., sarcoma, lymphoma, carcinoid, squamous cell carcinoma) or synchronous colon cancer.
• Presence of measurable lesions that meet RECIST v1.1 criteria for evaluation.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Estimated life expectancy \> 6 months.

You may not qualify if:

• Patients of dMMR or MSI-H status.
• Unexplained myelosuppression.
• Evidence of distant metastasis and inguinal lymph node metastasis based on comprehensive chest and abdominal CT or whole-body PET-CT scans. Retroperitoneal lymph nodes above the iliac vessel bifurcation are considered distant metastasis.
• Active autoimmune disease or history of autoimmune disease.
• Uncontrolled cardiac symptoms or diseases.
• History of other malignancies, except for cured basal cell carcinoma of the skin and cervical carcinoma in situ.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

trifluridine tipiracil drug combination; Capecitabine

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; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jinbo Yue, Docter

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinbo Yue, Docter

CONTACT

0531-67626442; jbyue@sdfmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Radiation Oncology Department

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: February 27, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 28, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)