Clinical trial NCT06850090: Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102
Official title: Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102 (Neo-REACT): A Multi-center, Randomized, Phase III Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Rectal Cancer
Rectal Cancer Patients
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2025-02-27
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Neoadjuvant fluoropyrimidine-based chemoradiotherapy (nCRT) followed by TME is the standard care for LARC. However, the tumor responses to nCRT cover a wide spectrum and the complete pathologic response rate varies from 8% to 20%. The low rate of pCR after neoadjuvant therapy could not satisfy patients with distal rectal cancer who want to keep anal function. Therefore, currently, the addition of other agents to 5-FU or capecitabine as components of the multimodality treatment for LARC outside of clinical trials is not recommended in clinical practice. TAS-102 is a new oral anti-tumor oral formulation of nucleoside analogue, FTD, and a thymidine phosphorylase inhibitor, TPI. TPI improves the bioavailability and ensures sufficient blood concentrations of FDT. 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 criteria: Inclusion Criteria:

1. Patients aged between 18 and 75 years of either sex.
2. Histologically confirmed rectal adenocarcinoma with the following conditions:

   1. Clinical stage II (T3-4, N-) or III (any T, N+) as determined by MRI.
   2. 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 \[≤5 cm from the anal verge\]).
3. No other types of rectal cancer (e.g., sarcoma, lymphoma, carcinoid, squamous cell carcinoma) or synchronous colon cancer.
4. Presence of measurable lesions that meet RECIST v1.1 criteria for evaluation.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
6. Estimated life expectancy \> 6 months.

Exclusion Criteria:

1. Patients of dMMR or MSI-H status.
2. Unexplained myelosuppression.
3. 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.
4. Active autoimmune disease or history of autoimmune disease.
5. Uncontrolled cardiac symptoms or diseases.
6. History of other malignancies, except for cured basal cell carcinoma of the skin and cervical carcinoma in situ.

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: 1 year
Secondary outcomes:
measure: The incidence of 3-4 grade adverse reactions
timeFrame: 1 year
measure: 3-year recurrence-free survival (RFS)
timeFrame: 3 year
measure: 3-year overall survival (OS)
timeFrame: 3 year
Other outcomes:
Locations:
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute
state: Shandong
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Jinbo Yue, Docter
role: PRINCIPAL_INVESTIGATOR
References: