Neoadjuvant Moderately Hypofractionated Radiotherapy Combined With Chemotherapy and Immunotherapy for High-risk pMMR/MSS Locally Advanced Rectal Cancer: A Prospective, Multi-center Randomized Control Phase II Trial

April 7, 2026 updated by: Xu jianmin, Fudan University
This study aims to observe and evaluate the efficacy and safety of moderately hypofractionated radiotherapy combined with chemotherapy and immunotherapy, compared with conventional neoadjuvant chemoradiotherapy, in patients with high-risk locally advanced colorectal cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
165

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China, 200032
        • Zhongshan hosptial, Fudan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years and ≤ 75 years.
  • Histologically confirmed colorectal adenocarcinoma with the lower margin of the lesion ≤ 10 cm from the anal verge as assessed by MRI, and immunohistochemistry confirming pMMR, or genetic testing demonstrating MSI-L or MSS.
  • Presence of at least one of the following high-risk factors as assessed by pelvic MRI: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph node (longest diameter > 7 mm).
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
  • No prior surgery, radiotherapy, chemotherapy, or targeted therapy.
  • Able to tolerate radiotherapy, chemotherapy, and immunotherapy: ECOG performance status score 0-2. Laboratory results: white blood cell count ≥ 4.0 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 80 g/L, ALT < 2 × ULN, total bilirubin < 35 μmol/L, serum creatinine < 1.5 × ULN or creatinine clearance ≥ 50 mL/min, thyroid-stimulating hormone within normal range (patients with stable thyroid function after hormone replacement therapy may be enrolled).
  • Willing to participate and able to provide written informed consent.

Exclusion Criteria:

  • Presence of distant metastasis.
  • Patients with stage I or II rectal cancer who do not require preoperative neoadjuvant therapy.
  • Severe diseases involving the heart, lung, brain, kidney, gastrointestinal tract, or other systemic conditions.
  • Untreated chronic hepatitis B or HBV carriers with HBV DNA > 500 IU/mL, or patients positive for HCV RNA. Patients with inactive hepatitis B surface antigen (HBsAg) carriers, those with hepatitis B who have been treated and are stable (HBV DNA < 500 IU/mL), and those who have been cured of hepatitis C may be enrolled.
  • Active autoimmune disease or history of autoimmune disease with potential for relapse.
  • Receipt of corticosteroids (at a dose equivalent to prednisone > 10 mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration.
  • History of thyroid dysfunction.
  • Severe chronic or active infection requiring systemic antifungal or antiviral therapy, including tuberculosis infection.
  • History of allergic constitution or allergy to multiple drugs.
  • History of prior pelvic radiotherapy.
  • History of inflammatory bowel disease.
  • Unwillingness to participate or inability to provide written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental group A
CapOx+Serplulimab+Moderately Hypofractionated Radiotherapy
Drug: Serplulimab

CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle.

Serplulimab: 300 mg intravenously on day 1 of each 21-day cycle. Long-course Concurrent Chemoradiotherapy：Delivered using a conventional fractionation schedule.Gross tumor volume (GTV): 1.8-2.0 Gy per fraction, total dose 50-50.4 Gy.Clinical target volume (CTV): 1.8 Gy per fraction, total dose 45 Gy.Once daily, 5 fractions per week.GTV receives 25-28 fractions; CTV receives 25 fractions.
Experimental: Experimental group B
CapOx+Serplulimab+Long-course radiotherapy
Radiation: Moderately Hypofractionated Radiotherapy

CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle.

Serplulimab: 300 mg intravenously on day 1 of each 21-day cycle. Moderately Hypofractionated Radiotherapy：Delivered using a simultaneous integrated boost (SIB) technique.Gross tumor volume (GTV): 3.5 Gy per fraction; clinical target volume (CTV): 3.0 Gy per fraction.Once daily, 5 fractions per week, for a total of 10 fractions.Total dose: GTV 35 Gy, CTV 30 Gy.
Active Comparator: Control arm
CapOx+Long-course radiotherapy
Other: CapOx+Long-course radiotherapy

CapOx Regimen Recommended Dose：Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle.Oxaliplatin: 130 mg/m² intravenously on day 1 of each 21-day cycle.

Long-course Concurrent Chemoradiotherapy：Delivered using a conventional fractionation schedule.Gross tumor volume (GTV): 1.8-2.0 Gy per fraction, total dose 50-50.4 Gy.Clinical target volume (CTV): 1.8 Gy per fraction, total dose 45 Gy.Once daily, 5 fractions per week.GTV receives 25-28 fractions; CTV receives 25 fractions.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Complete Remission (CR) Rate
Time Frame: At the time of surgery for pCR, and at 1 year after achieving cCR for sustained cCR

Definition: The proportion of participants achieving complete remission, defined as:

Pathologic complete response (pCR): No residual viable tumor cells detected in the resected specimen after neoadjuvant treatment (ypT0N0) Sustained clinical complete response (cCR): No evidence of residual tumor on digital rectal examination, endoscopy, and MRI, maintained for more than 1 year without surgery Assessment Method: Evaluated by investigators based on imaging, endoscopic findings, pathology (for surgical cases), and clinical examination
At the time of surgery for pCR, and at 1 year after achieving cCR for sustained cCR

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
AE rate
Time Frame: 24months
Adverse event incidence rate
24months
3-Year Disease-Free Survival (DFS) Rate
Time Frame: Up to 3 years after randomization
Time from randomization to evidence of disease recurrence within 3 years
Up to 3 years after randomization
3-Year Overall Survival (OS) Rate
Time Frame: up to 5 years
Time from randomization to death from any cause.
up to 5 years
3-Year Event-Free Survival (EFS) Rate
Time Frame: up to 3 years from treatment
Defined as the time from the start of treatment to the occurrence of any of the following events, whichever occurs first: disease progression that precludes surgery, postoperative disease progression or recurrence (per RECIST v1.1), or death from any cause.
up to 3 years from treatment
Objective Response Rate
Time Frame: Up to 1 years
The rate of participants that achieve either a complete response (CR) or a partial response (PR).
Up to 1 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Quality of life (QoL)
Time Frame: From date of randomization until the date of death from any cause, assessed up to 10 years
Quality of life will be evaluated using the European O-rganization for Reasearch and Treatment of Cancer Quality of Life Questionnaire-C30（EORTC QLQ-C30） (range 0-100). It evaluates the quality of life from 30 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.
From date of randomization until the date of death from any cause, assessed up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KY2026078

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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