Umbrella Trial of Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

March 25, 2026 updated by: Zhen Zhang, Fudan University

An Exploratory Umbrella Trial of Neoadjuvant Therapy for Locally Advanced Colorectal Cancer Based on Molecular Subtypes

This is a prospective, open-label, single-center, phase II umbrella trial designed to evaluate the efficacy and safety of neoadjuvant therapy for locally advanced colorectal cancer. Patients will be stratified into four cohorts based on microsatellite instability (MSI) status, KRAS mutation status, and the consensus molecular subtypes (CMS). Six arms are included across four cohorts and each arm will be assigned to a specific treatment regimen. The primary endpoint is the complete response rate. Secondary endpoints include safety, organ preservation rate (for rectal cancer only), R0 resection rate, surgical complications, treatment compliance, 3-year survival, and quality of life (QoL) score.

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.
134

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 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 Contact Backup

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:

  1. Age 18-75 years old, female and male;
  2. Pathological confirmed adenocarcinoma;
  3. Stage II/III colon cancer, or stage II/III rectal cancer located less than 10 cm from the anal verge;
  4. Treatment-naïve and no distance metastases;
  5. KPS ≥ 70;
  6. No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
  7. Baseline blood and biochemical indicators meet the following criteria: neutrophils ≥ 1.5 × 10^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10^9/L, ALT/ AST ≤ 2.5 ULN, Cr ≤ 1 ULN;
  8. With good compliance and signed the consent form.

Exclusion Criteria:

  1. Pregnancy or breast-feeding women;
  2. Known history of other malignancies within 5 years;
  3. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
  4. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
  5. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
  6. Uncontrolled infection which needs systemic therapy;
  7. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
  8. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
  9. Allergic to any component of the therapy.

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: MSI-H/dMMR
Drug: SHR-1701
1800mg d1 q3w
Drug: SHR-8068
280mg，C1D1
Experimental: MSS-KRAS G12C-Adebrelimab
Radiation: Short-course radiotherapy
25Gy/5Fx
Drug: XELOX (Capecitabine and Oxaliplatin)
Oxaliplatin: 130mg/m2 d1 q3w Capecitabine: 1000mg/m2 bid d1-14 q3w
Drug: PD-L1 antibody
1200mg d1 q3w
Drug: HRS-7058
200mg bid
Experimental: MSS-KRAS G12C-cetuximab β
Radiation: Short-course radiotherapy
25Gy/5Fx
Drug: XELOX (Capecitabine and Oxaliplatin)
Oxaliplatin: 130mg/m2 d1 q3w Capecitabine: 1000mg/m2 bid d1-14 q3w
Drug: HRS-7058
200mg bid
Drug: cetuximab β
250mg/m2 d1, 500mg/m2 d8 q3w
Experimental: MSS-KRAS G12D-Adebrelimab
Radiation: Short-course radiotherapy
25Gy/5Fx
Drug: XELOX (Capecitabine and Oxaliplatin)
Oxaliplatin: 130mg/m2 d1 q3w Capecitabine: 1000mg/m2 bid d1-14 q3w
Drug: PD-L1 antibody
1200mg d1 q3w
Drug: HRS-4642
500mg d1, 1200mg d8 q3w
Experimental: MSS-KRAS G12D-cetuximab β
Radiation: Short-course radiotherapy
25Gy/5Fx
Drug: XELOX (Capecitabine and Oxaliplatin)
Oxaliplatin: 130mg/m2 d1 q3w Capecitabine: 1000mg/m2 bid d1-14 q3w
Drug: cetuximab β
250mg/m2 d1, 500mg/m2 d8 q3w
Drug: HRS-4642
500mg d1, 1200mg d8 q3w
Experimental: MSS-CMS
Drug: SHR-1701
1800mg d1 q3w
Radiation: Short-course radiotherapy
25Gy/5Fx
Drug: XELOX (Capecitabine and Oxaliplatin)
Oxaliplatin: 130mg/m2 d1 q3w Capecitabine: 1000mg/m2 bid d1-14 q3w

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
Time Frame
Complete response (CR) rate: rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W&W strategy.
Time Frame: 1 month after the surgery or 1 year after the decision of W&W.
1 month after the surgery or 1 year after the decision of W&W.

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
Adverse effects rate: proportion of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0.
Time Frame: From date of stratification to 3 months post-neoadjuvant therapy, an average of 8 months.
From date of stratification to 3 months post-neoadjuvant therapy, an average of 8 months.
Organ preservation rate: proportion of participants who either achieve cCR and choose W&W or achieve cCR/near-cCR and choose local excision, out of the total participants who complete neoadjuvant therapy.
Time Frame: From date of stratification until the resection of rectum or anus, assessed up to 36 months.
This endpoint is applicable only to patients with locally advanced rectal cancer.
From date of stratification until the resection of rectum or anus, assessed up to 36 months.
R0 resection rate: proportion of surgical resections with negative margins (proximal, distal, and circumferential) on microscopic examination, with CRM negativity defined as > 1 mm from tumor bed.
Time Frame: 1 month after the surgery.
1 month after the surgery.
Rate of surgical complications: rates of surgical complications such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
Time Frame: within 3 months after the surgery.
within 3 months after the surgery.
Treatment compliance: treatment completion rate and delay duration during the treatment period.
Time Frame: From date of stratification to the completion of neoadjuvant therapy, an average of 5 months.
From date of stratification to the completion of neoadjuvant therapy, an average of 5 months.
3 year local recurrence free survival rate: proportion of participants with no tumor recurrence in the primary site (e.g., rectum) or other pelvic regions within 3 years from date of surgery or cCR.
Time Frame: From date of surgery or cCR until the date of first documented pelvic failure, assessed up to 36 months.
From date of surgery or cCR until the date of first documented pelvic failure, assessed up to 36 months.
3 year distant metastasis free survival rate: proportion of participants with no distant metastases (e.g., liver, lung) within 3 years from date of stratification.
Time Frame: From date of stratification until the date of first documented distant metastasis, assessed up to 36 months.
From date of stratification until the date of first documented distant metastasis, assessed up to 36 months.
3 year disease free survival rate: proportion of participants with no disease recurrence (including local recurrence and distant metastasis) or death from the disease within 3 years from date of stratification.
Time Frame: From date of stratification until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
From date of stratification until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
3 year overall survival rate: proportion of participants who are alive at 3 years from date of stratification.
Time Frame: From date of stratification until the date of death from any cause, assessed up to 36 months.
From date of stratification until the date of death from any cause, assessed up to 36 months.
Quality of life (QoL) score: subjective assessment using validated standardized questionnaires.
Time Frame: From date of stratification to 3 years post-neoadjuvant therapy.
From date of stratification to 3 years post-neoadjuvant therapy.

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.
April 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.
April 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.
April 1, 2030

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).
March 20, 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.
March 25, 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.
March 31, 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.
March 31, 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.
March 25, 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.
  • 2025-697-4846

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

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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