Rectal CancerPhase 3NCT06850090
Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102 (Neo-REACT): A Multi-center, Randomized, Phase III Trial
A Phase 3 study testing TAS-102 and Capecitabine in people with Rectal Cancer and Rectal Cancer Patients, run by Shandong Cancer Hospital and Institute at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer, Rectal Cancer Patients
- What is being tested?
- TAS-102 and Capecitabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 1 siteChina
- Study dates
- 30 Jul 2025to Jun 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shandong Cancer Hospital and Institute
Jinan, Shandong
Jinbo Yue, Doctor, 0531-67626442, jbyue@sdfmu.ed
About this study
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.
Read the 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.
- Conditions
- Rectal Cancer, Rectal Cancer Patients
- Being tested
- TAS-102, Capecitabine
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAS-102Combination product
Radiotherapy:
- Radiotherapy Technique: Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), or volume modulated arc therapy (VMAT);
- 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 9 cycles.
Surgery:
The operation follows the principle of TME. The type of surgery depends on the location and extent of the primary tumor.
CapecitabineCombination product
Radiotherapy:
- Radiotherapy Technique: Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), or volume modulated arc therapy (VMAT);
- 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 6 cycles.
Surgery:
The operation follows the principle of TME. The type of surgery depends on the location and extent of the primary tumor.
| Study group | Role | What they receive |
|---|---|---|
| TAS-102 group | Experimental | Neoadjuvant long-course radiotherapy combined with TAS-102 Receives: Combination Product: TAS-102 |
| Capecitabine group | Active comparator | Neoadjuvant long-course radiotherapy combined with capecitabine Receives: Combination Product: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (3)
The incidence of 3-4 grade adverse reactions
The adverse reactions are graded and recorded according to the National Cancer Institute General Terminology for Adverse Events (CTCAE) Version 5.0.
Measured: 1 year
3-year recurrence-free survival (RFS)
3-year RFS is measured from randomization to the first occurrence of recurrence or last follow-up.
Measured: 3 year
3-year overall survival (OS)
3-year OS is measured from randomization to death due to any cause or last follow-up.
Measured: 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2025
- Study start30 Jul 2025
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong Cancer Hospital and Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinbo Yue, Shandong Cancer Hospital and Institute
- Investigators
- Jinbo Yue, Docter, Principal investigator, Shandong Cancer Hospital and Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06850090
- Sponsor's protocol ID
- SDZLEC2025-026-02
- Status last verified
- Oct 2026
- First submitted
- 19 Feb 2025
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Radiotherapy for Rectal Adenocarcinoma With Capecitabine Versus TAS-102 (Neo-REACT): A Multi-center, Randomized, Phase III Trial
- ClinicalTrials.gov ID
- NCT06850090
- Acronym / sponsor ID
- SDZLEC2025-026-02
- Conditions
- Rectal Cancer, Rectal Cancer Patients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Shandong Cancer Hospital and InstituteUniversity, hospital or other
- Study start
- 30 Jul 2025 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 27 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TAS-102 group | Experimental | Combination Product: TAS-102Neoadjuvant long-course radiotherapy combined with TAS-102 |
| Capecitabine group | Active comparator | Combination Product: CapecitabineNeoadjuvant long-course radiotherapy combined with capecitabine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients aged between 18 and 75 years of either sex.
- Histologically confirmed rectal adenocarcinoma with the following conditions:
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAS-102Radiotherapy: 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 9 cycles. Surgery: The operation follows the principle of TME. The type of surgery depends on the location and extent of the primary tumor. | Combination product | TAS-102 group |
| CapecitabineRadiotherapy: 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 6 cycles. Surgery: The operation follows the principle of TME. The type of surgery depends on the location and extent of the primary tumor. | Combination product | Capecitabine group |
Primary outcome
Complete response (CR) rate
Time frame: 1 year
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.
3 secondary outcomes
The incidence of 3-4 grade adverse reactions
Time frame: 1 year
3-year recurrence-free survival (RFS)
Time frame: 3 year
3-year overall survival (OS)
Time frame: 3 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jinbo Yue, Docter principal investigator
Shandong Cancer Hospital and Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TAS-102 and Capecitabine in people with Rectal Cancer and Rectal Cancer Patients, run by Shandong Cancer Hospital and Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jinbo Yue, Docter (0531-67626442, jbyue@sdfmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response (CR) rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.