Efficacy and Safety Exploration of Short Course Radiotherapy Followed by Surufatinib and Toripalimab in Neoadjuvant Treatment of Locally Advanced Rectal Cancer (STARS-RC08)

November 6, 2026 updated by: Pengyu Chang, The First Hospital of Jilin University

Why is this study conducted? The purpose of this study is to improve treatment efficacy, particularly the pathological complete response rate, in patients with high-risk/extremely high-risk locally advanced rectal cancer (LARC). While advances have been achieved with neoadjuvant chemoradiotherapy combined with immunotherapy in recent years, regional recurrence and distant metastasis remain unresolved. New therapeutic strategies for this patient population are therefore urgently needed.

Rectal cancer management typically includes surgery, radiation therapy and chemotherapy. Treatment paradigms are shifting toward neoadjuvant chemoradiotherapy plus immunotherapy, which has demonstrated promising potential in several clinical trials. These data indicate that short-course radiotherapy combined with anti-angiogenic agents and immune checkpoint inhibitors may improve patient prognosis and tumor response. Nevertheless, the efficacy and safety of this regimen in high-risk patients require further validation.

Against this background, the study evaluates a novel regimen of short-course radiotherapy followed by surufatinib and toripalimab (anti-PD-1) to raise the pathological complete response rate. The investigators also explore efficacy-related biomarkers including RAS/BRAF status and gene expression profiles to support personalized treatment. This study aims to optimize therapy for LARC patients and inform future treatment strategies.

Why are participants invited to participate in this study? Participants are considered eligible for enrollment upon diagnosis of high-risk or extremely high-risk locally advanced rectal cancer consistent with study inclusion criteria. Eligibility requires confirmed pathological diagnosis, appropriate tumor location, and absence of severe comorbidities or exclusionary diseases (e.g., recurrent rectal cancer, cardiac dysfunction). Final enrollment decisions are made by study physicians based on individual clinical conditions.

What do participants need to do to participate in this study? Study participation requires adherence to predefined procedures. Participants receive scheduled medical assessments including blood tests, imaging scans and anorectal function evaluation. During the study period, participants may complete questionnaires and provide biospecimens (e.g., blood samples) for efficacy analysis. The study team defines the frequency and content of each follow-up to maintain continuous monitoring throughout treatment. Compliance with study procedures supports evaluation of regimen efficacy.

What are the risks of participating in this study?

This study applies neoadjuvant short-course radiotherapy, anti-PD-1 monoclonal antibody (toripalimab), and anti-angiogenic therapy (surufatinib). Potential risks for participants are listed below:

Risk of neoadjuvant short-course radiotherapy: Participants may develop grade ≥3 adverse events including, but not limited to, severe diarrhea, grade 3 neutropenia and grade 3 radiation dermatitis, which may impair quality of life.

Risk of anti-PD-1 monoclonal antibody: Toripalimab may induce immune-related adverse events (irAEs) across organ systems. Common irAEs include skin toxicity (papules, pruritus; incidence 30%-40%), diarrhea/colitis (8%-19%), fatigue (16%-24%), immune-related hepatitis (5%), hypothyroidism (4%-10%), and hyperthyroidism (4%). Approximately two-thirds of patients receiving immune checkpoint inhibitors develop irAEs of varying severity, and serious adverse events are non-negligible.

Risk of anti-angiogenic therapy: Surufatinib may trigger adverse events related to anti-angiogenic and immunomodulatory effects. Common adverse events (incidence >20%) include proteinuria, hypertension, bleeding, liver dysfunction and diarrhea. Among grade ≥3 adverse events, hypertension (29.7%), proteinuria (14.5%), liver dysfunction (12.8%) and bleeding (4.5%) predominate. Rarely, treatment-related death may occur secondary to gastrointestinal hemorrhage or cerebral hemorrhage.

Handling of research related injuries? This interventional study introduces no extra risks beyond standard clinical care. Any harm arising from study participation will be addressed for compensation and liability in accordance with applicable laws and regulations.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
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.

Detailed Description

Why is this study conducted? The purpose of this study is to improve treatment efficacy, particularly the pathological complete response rate, in patients with high-risk/extremely high-risk locally advanced rectal cancer (LARC). Recent advances have been achieved with neoadjuvant chemoradiotherapy combined with immunotherapy for rectal cancer, yet regional recurrence and distant metastasis remain persistent challenges. Developing novel therapeutic strategies for this patient population is therefore critical.

Rectal cancer management typically consists of surgery, radiation therapy, and chemotherapy. Treatment strategies are gradually shifting toward neoadjuvant chemoradiotherapy plus immunotherapy, which has demonstrated promising potential in multiple clinical trials. These trials indicate that combining short-course radiotherapy, anti-angiogenic agents, and immune checkpoint inhibitors may improve patient prognosis and increase tumor response rates. Nonetheless, the efficacy and safety of such regimens in high-risk patients require further validation.

Against this background, the study aims to evaluate a novel regimen: short-course radiotherapy followed by surufatinib and toripalimab (anti-PD-1), to increase the pathological complete response rate. The investigators also explore efficacy-associated biomarkers including RAS/BRAF status and gene expression profiles to support personalized treatment. This study seeks to optimize therapy for patients with LARC and inform future treatment approaches.

Why are participants invited to participate in this study? Participants are eligible for screening with a diagnosis of high-risk or extremely high-risk locally advanced rectal cancer that satisfies study inclusion criteria. Eligible candidates must have pathologically confirmed disease, appropriate tumor location, and no severe comorbidities or exclusionary illnesses (e.g., recurrent rectal cancer, cardiac dysfunction). Final enrollment decisions are made by study physicians based on individual clinical status.

What do participants need to do to participate in this study? Study participation requires adherence to predefined study procedures. Participants receive scheduled medical assessments, including blood tests, imaging scans, and anorectal function evaluations. During the study period, participants may complete questionnaires and provide biospecimens (e.g., blood samples) for treatment efficacy analysis. The study team defines the frequency and content of each follow-up to maintain continuous monitoring throughout treatment. Compliance with study procedures supports evaluation of regimen efficacy.

What are the risks of participating in this study?

This study applies neoadjuvant short-course radiotherapy, anti-PD-1 monoclonal antibody (toripalimab), and anti-angiogenic therapy (surufatinib). Potential risks for participants are listed below:

Risk of neoadjuvant short-course radiotherapy: Participants may develop grade ≥3 adverse events including, but not limited to, severe diarrhea, grade 3 neutropenia, and grade 3 radiation dermatitis, which may impair patient quality of life.

Risk of anti-PD-1 monoclonal antibody: Toripalimab may induce immune-related adverse events (irAEs) involving any organ system. Common irAEs include skin toxicity (papules, pruritus; incidence 30% to 40%), diarrhea and/or colitis (8% to 19%), fatigue (16% to 24%), immune-related hepatitis (5%), hypothyroidism (4% to 10%), and hyperthyroidism (4%). Approximately two-thirds of patients receiving immune checkpoint inhibitors develop irAEs of varying severity; the risk of serious adverse events cannot be overlooked.

Risk of anti-angiogenic therapy: Surufatinib may trigger adverse reactions related to its anti-angiogenic and immunomodulatory effects. Common adverse events (incidence >20%) include proteinuria, hypertension, bleeding, liver dysfunction, and diarrhea. Among grade ≥3 adverse events, hypertension (29.7%), proteinuria (14.5%), liver dysfunction (12.8%), and bleeding (4.5%) occur most frequently. Rarely, treatment-related death may result from gastrointestinal hemorrhage or cerebral hemorrhage.

Handling of research related injuries? This interventional study introduces no incremental risks beyond standard clinical diagnosis and treatment. Any harm arising from study participation will be reviewed for compensation and liability in accordance with applicable laws and regulations.

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.
32

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
  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Jilin
      • Changchun, Jilin, China, 130000
        • Recruiting
        • the first hospital of Jilin 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

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18-75 years, male or female
  • Pathologically confirmed rectal tubular adenocarcinoma, Grade 1 (well), Grade 2 (moderate), or Grade 3 (poor) differentiation; pMMR phenotype
  • Mid or low rectal cancer with the lower tumor margin within 10 cm of the anal verge
  • Treatment-naive disease with high-risk features including cT4, cN2, MRF+, or EMVI+; and/or mrLR4 disease with impossible anal preservation or mrLR3 disease with difficult anal preservation at baseline assessment
  • No evidence of distant metastasis
  • ECOG performance status 0-1

Exclusion Criteria:

  • Recurrent rectal cancer
  • ECOG performance status ≥2
  • Other organ diseases that create unacceptable treatment risk (refer to the protocol for full exclusion criteria)

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: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group 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: short course radiotherapy followed by surufatinib and toripalimab in locally advanced rectal cancer
Radiation: radiotherapy

Short-course preoperative radiotherapy (SCRT) for locally advanced rectal cancer.

Drug: Toripalimab

Toripalimab 200 mg will be administered intravenously once every 21 days for 4 cycles.

Drug: Surufatinib 250mg/d qd once daily

Surufatinib 250 mg will be orally administered once daily during the first 3 cycles concurrently with toripalimab.

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
Pathologic complete response (pCR) rate
Time Frame: From baseline up to the time of surgery (approximately 14 weeks after radiotherapy initiation)

Pathologic complete response (pCR) rate is defined as the percentage of patients who achieve pCR after neoadjuvant therapy within the eligible population [15].

Pathologic complete response (pCR) is characterized by the absence of invasive cancer in the primary rectum and negative regional lymph nodes following adequate or complete sampling (ypT0N0, tumor regression grade [TRG] 0 points) [16]. Microscopically, cancer cells in the tumor bed are absent, with possible infiltration of inflammatory cells in the interstitium. Additionally, foamy cells and fibrous tissue proliferation may be observed. (For evaluation criteria, refer to the AJCC 8th Edition: Colorectal Cancer.)
From baseline up to the time of surgery (approximately 14 weeks after radiotherapy initiation)

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.
The First Hospital of Jilin 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 (Actual)

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.
May 16, 2025

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.
December 31, 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.
December 31, 2028

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).
May 15, 2025

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.
November 6, 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.
November 13, 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.
November 13, 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.
November 6, 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.
June 1, 2026

More Information

Terms related to this study

Keywords

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.

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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