Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102 (Neo-REACT): A Multi-center, Randomized, Phase III Trial
Shandong Cancer Hospital and Institute
210 participants
Jul 30, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria8
- 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.
Exclusion Criteria6
- 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.
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Interventions
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).
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)
Locations(1)
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NCT06850090