Immune Checkpoint TherapyPhase 2/3NCT06958419

Node-Sparing Short-Course Radiotherapy Plus Chemotherapy, Bevacizumab and PD-1 Inhibitor in Metastatic pMMR/MSS Colorectal Cancer (MODIFI-CRC)

A Phase 2/3 study testing Node-Sparing Radiotherapy plus first-line therapy and First-line treatment in people with Immune Checkpoint Therapy and Radiotherapy, run by Sixth Affiliated Hospital, Sun Yat-sen University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Immune Checkpoint Therapy, Radiotherapy, Metastatic Colorectal Cancer (CRC)
What is being tested?: Node-Sparing Radiotherapy plus first-line therapy and First-line treatment
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 286 participants
Where: 1 siteChina
Study dates: 1 May 2025to 31 Dec 2031
Phase: Phase 2/3
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

Voluntarily signs a written informed consent form.
Aged between 18 and 75 years at the time of enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Expected survival of more than 3 months.
Histologically or cytologically confirmed colorectal adenocarcinoma.
Patients must be considered unsuitable for curative surgical resection or local treatment and must not have received prior systemic anti-tumor therapy for recurrent or metastatic disease. Patients with prior neoadjuvant or adjuvant therapy may be enrolled if recurrence or metastasis occurs ≥12 months after the last dose of such treatment.

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At least one measurable lesion per RECIST v1.1 that can be accurately measured repeatedly. Note: Brain metastases cannot be used as target lesions.
Able to provide 10-20 unstained tumor tissue FFPE slides from recent biopsy or archival material stored within 3 years. Ten slides will be used for immunohistochemistry and ten for genomic testing (recent biopsy preferred). If samples are of insufficient quality (as determined by the central lab), additional slides may be required. If adequate slides cannot be provided, partial or full waiver may be granted upon approval by the medical monitor.
Agrees to provide tumor tissue and peripheral blood samples during screening and throughout the study for research purposes.
Adequate organ function as defined below:
Hematologic (no use of blood products or growth factors within 7 days prior to treatment):
Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
Platelet count ≥ 100 × 10⁹/L
Hemoglobin ≥ 90 g/L
Renal:
Calculated creatinine clearance (CrCl) ≥ 50 mL/min (Cockcroft-Gault formula: CrCl = [(140 - age) × weight (kg) × 0.85 (if female)] / [72 × serum creatinine (mg/dL)])
Urine protein < 2+ on dipstick or < 1.0 g per 24-hour urine collection
Hepatic:
Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN)
AST and ALT ≤ 2.5 × ULN
Serum albumin ≥ 28 g/L
Coagulation:
International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
Cardiac:
Left ventricular ejection fraction (LVEF) ≥ 50%
Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to initiating study treatment. If the urine test is inconclusive, a serum test must confirm the result. Women of childbearing potential engaging in sexual activity with non-sterilized male partners must agree to use acceptable contraception from screening through 120 days after the last dose of study drug. The decision to discontinue contraception beyond this period should be discussed with the investigator. Periodic abstinence and the rhythm method are not acceptable.
Women of childbearing potential are defined as those who have not undergone surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and have not been postmenopausal (defined as at least 12 consecutive months of amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range).
Highly effective contraception methods are those with a failure rate of <1% per year when used consistently and correctly. In addition to barrier methods, hormonal contraception (e.g., oral contraceptives) must also be used.
Willing and able to comply with scheduled visits, treatment procedures, laboratory tests, and other protocol requirements.

Who cannot join

• Known MSI-H or dMMR status.
History of other malignancies within the past 3 years, except for those cured by local treatment, such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or ductal carcinoma in situ of the breast.
Prior immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), immune agonists (e.g., ICOS, CD40, CD137, GITR, OX40), or immune cell-based therapies targeting tumor immunity.
Prior adjuvant or neoadjuvant therapy targeting EGFR or VEGF/VEGFR pathways (e.g., bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, or biosimilars).
Active CNS metastases. Patients with previously treated brain metastases may be eligible if clinically stable for at least 2 weeks (from the first dose of study drug) and off corticosteroids for at least 3 days prior to treatment. Patients with untreated, asymptomatic brain metastases (no neurologic symptoms, no corticosteroids, and all lesions ≤ 1.5 cm in longest diameter) may enroll but require regular CNS monitoring.
Known brainstem, meningeal, or spinal cord metastases or compression.

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Symptomatic or recurrently drained pleural effusion, pericardial effusion, or ascites.
Prior systemic or local anti-tumor therapy for locally advanced rectal cancer, including curative surgery, chemotherapy, radiotherapy, immunotherapy, biologics, or small-molecule targeted therapy.
Receipt of nonspecific immunomodulators (e.g., interleukins, interferons, thymic peptides, TNF) within 2 weeks prior to study treatment (except IL-11 for thrombocytopenia), or anti-tumor traditional Chinese medicine within 1 week prior to study treatment.
Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., with corticosteroids, immunosuppressants, or DMARDs). Replacement therapy (e.g., thyroid hormone, insulin, or physiologic corticosteroids for adrenal/pituitary insufficiency) is allowed.
History of non-infectious pneumonitis requiring systemic corticosteroids, or current interstitial lung disease.
History of bleeding disorders or coagulopathy; long-term anticoagulation (e.g., atrial fibrillation with CHADS2 score ≥ 2).
Uncontrolled comorbidities including, but not limited to, decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric/social conditions impairing protocol compliance or informed consent.
History of myocarditis, cardiomyopathy, or malignant arrhythmias; unstable angina, congestive heart failure, or vascular disease (e.g., aortic aneurysm requiring repair or DVT) requiring hospitalization within 12 months. Other cardiovascular conditions affecting drug safety (e.g., poorly controlled arrhythmias, myocardial infarction, or ischemia) are excluded.
Within 6 months prior to study treatment: gastroesophageal varices, severe ulcers, unhealed wounds, GI perforation, fistulas, obstruction, intra-abdominal abscess, or acute GI bleeding.
Within 6 months prior to treatment: arterial thromboembolism, venous thromboembolism (grade ≥3, NCI-CTCAE v5.0), TIA, stroke, hypertensive crisis, or hypertensive encephalopathy.
COPD exacerbation within 1 month before study treatment; uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg despite oral medications).
Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).
Serious infections within 4 weeks before treatment, including those requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic antibiotics within 10 days before treatment (excluding antiviral therapy for hepatitis B or C).
Major surgery or significant trauma within 30 days prior to treatment; minor local surgery within 3 days (excluding PICC line placement).
History of immunodeficiency; HIV antibody positivity; long-term use of systemic corticosteroids or immunosuppressants.
Known active tuberculosis (TB) or suspected active TB not ruled out by clinical evaluation (e.g., sputum testing, chest imaging); known active syphilis.
History of allogeneic organ or hematopoietic stem cell transplantation.
Untreated active hepatitis B infection (HBsAg-positive with HBV DNA > 1,000 copies/mL or >200 IU/mL); patients with chronic hepatitis B must receive antiviral therapy during the study. Active hepatitis C (HCV antibody-positive with detectable HCV RNA) is also excluded.
Receipt of a live vaccine within 30 days before treatment or planned live vaccination during the study.
Known allergy to any component of the study drugs or history of serious hypersensitivity to monoclonal antibodies.
Known psychiatric disorders, substance abuse, alcoholism, or drug dependence.
Pregnant or breastfeeding women.
Any condition, treatment, or laboratory abnormality that may interfere with study results, prevent full participation, or not be in the participant's best interest.
Local or systemic disease caused by a benign tumor, or tumor-associated conditions causing high medical risk or survival uncertainty (e.g., leukemoid reaction with WBC > 20 × 10⁹/L, cachexia with >10% weight loss within 3 months prior to screening, or BMI ≤ 18).
Current evidence of significant gastrointestinal obstruction based on clinical or radiographic findings.
History of bleeding disorders or coagulopathy; radiographic evidence of tumor encasing major vessels or showing necrosis/cavitation that, in the investigator's judgment, may pose bleeding risk; continuous anticoagulation within 10 days prior to first dose.
Tumor invasion of critical organs or vessels (e.g., heart/pericardium, trachea, esophagus, aorta, or superior vena cava) with risk of complications such as fistulas (e.g., esophagotracheal, esophageal-pleural, or intestinal fistulas).
Presence of free intraperitoneal gas not attributable to recent puncture or local surgical procedure.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yanxin Luo, M.D., Ph.D. contact

+86-20-38254221

luoyx25@mail.sysu.edu.cn

Yikan Cheng contact

15102033641

China1 site, 1 recruiting

The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510655
Qian Wu, +86-020-38379764, zslyllb@mail.sysu.edu.cn
Recruiting

Other trials in China

About this study

Official title: Node-Sparing Short-Course Radiotherapy Followed by First-Line Chemotherapy Plus Bevacizumab and PD-1 Inhibitor Versus Chemotherapy Plus Bevacizumab Alone in Metastatic pMMR/MSS Colorectal Cancer: A Randomized, Phase II/III Trial (MODIFI-CRC)

The current standard first-line treatment for metastatic colorectal cancer is chemotherapy combined with targeted therapy, yet the prognosis remains poor. Although combining immunotherapy, anti-angiogenic agents, and chemotherapy has shown some efficacy in MSS/pMMR metastatic patients, progression-free survival (PFS) remains suboptimal. Radiotherapy-particularly high-dose radiotherapy-can enhance tumor antigen release and potentially improve the response of MSS/pMMR colorectal cancer to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for PD-1-mediated anti-tumor activity, but radiation-induced damage and fibrosis may impair their immune function. Prior studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This phase II/III study aims to evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and PD-1 blockade can improve objective response rate (ORR) in phase II and progression-free survival (PFS) in phase III, together with treatment tolerance, and overall prognosis in patients with pMMR/MSS metastatic colorectal cancer.

Conditions: Immune Checkpoint Therapy, Radiotherapy, Metastatic Colorectal Cancer (CRC)
Being tested: Node-Sparing Radiotherapy plus first-line therapy, First-line treatment
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Node-Sparing Radiotherapy plus first-line therapyCombination product
Patients will receive node-sparing modified short-course radiotherapy, followed by 8 cycles of FOLFOX chemotherapy combined with bevacizumab and a PD-1 inhibitor. After induction therapy, patients will continue with maintenance therapy using bevacizumab, PD-1 inhibitor, and 5-fluorouracil (5-FU), administered every 2 weeks (Q2W).
First-line treatmentCombination product
Patients will receive 8 cycles of FOLFOX chemotherapy combined with bevacizumab, followed by maintenance therapy with bevacizumab and 5-fluorouracil (5-FU), administered every 2 weeks (Q2W).

Study groups in NCT06958419
Study group	Role	What they receive
Node-sparing Radiotherapy Group	Experimental	Not described Receives: Combination Product: Node-Sparing Radiotherapy plus first-line therapy
First-line therapy Group	Active comparator	Not described Receives: Combination Product: First-line treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate(ORR)
Phase II: To evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and a PD-1 inhibitor can improve Objective Response Rate(ORR) in patients with metastatic pMMR/MSS colorectal cancer.
Measured: From initiation of treatment until disease progression or death, whichever occurs first, assessed over a period of up to 36 months
Progression-free survival (PFS)
Phase III: To evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and a PD-1 inhibitor can improve progression-free survival (PFS) in patients with metastatic pMMR/MSS colorectal cancer.
Measured: From initiation of treatment until disease progression or death, whichever occurs first, assessed over a period of up to 36 months

Secondary outcomes (5)

Duration of response
Measured: From the first documented occurrence of complete response (CR) or partial response (PR) to the first documented disease progression (per RECIST v1.1) or death from any cause, whichever occurs first, assessed over a period of up to 36 months
Disease control rate
Measured: From treatment start to the end of study at 3 years
Overall survival (OS) rate
Measured: From treatment start to the end of study at 3 years
Treatment related adverse effect
Measured: From treatment start to 30 days after the end of treatment
Time to response (TTR)
Measured: From randomization to the first documented occurrence of complete response (CR) or partial response (PR), assessed over a period of up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 May 202531 Dec 2031

First posted6 May 2025
Study start1 May 2025
Primary completion31 Dec 2030 (estimated)
Study completion31 Dec 2031 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Immune Checkpoint TherapyStudies of the same condition, open and under way.
More trials run by Sixth Affiliated Hospital, Sun Yat-sen UniversityThe sponsor's other registered studies.
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 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 286 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06958419
Sponsor's protocol ID: 2025ZSLYEC-418
Status last verified: Aug 2025
First submitted: 24 Apr 2025
Last updated: 7 Aug 2025
Results posted: No
Data monitoring committee: Yes
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 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Node-Sparing Short-Course Radiotherapy Followed by First-Line Chemotherapy Plus Bevacizumab and PD-1 Inhibitor Versus Chemotherapy Plus Bevacizumab Alone in Metastatic pMMR/MSS Colorectal Cancer: A Randomized, Phase II/III Trial (MODIFI-CRC)
ClinicalTrials.gov ID: NCT06958419
Acronym / sponsor ID: 2025ZSLYEC-418
Conditions: Immune Checkpoint Therapy, Radiotherapy, Metastatic Colorectal Cancer (CRC)
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 286 participants (estimated)
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen UniversityUniversity, hospital or other
Study start: 1 May 2025 (actual)
Primary completion: 31 Dec 2030 (estimated)
Study completion: 31 Dec 2031 (estimated)
First posted: 6 May 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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Node-sparing Radiotherapy Group	Experimental	Combination Product: Node-Sparing Radiotherapy plus first-line therapy
First-line therapy Group	Active comparator	Combination Product: First-line treatment

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (29 listed)

Voluntarily signs a written informed consent form.

Key exclusion criteria (34 listed)

• Known MSI-H or dMMR status.

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
Node-Sparing Radiotherapy plus first-line therapyPatients will receive node-sparing modified short-course radiotherapy, followed by 8 cycles of FOLFOX chemotherapy combined with bevacizumab and a PD-1 inhibitor. After induction therapy, patients will continue with maintenance therapy using bevacizumab, PD-1 inhibitor, and 5-fluorouracil (5-FU), administered every 2 weeks (Q2W).	Combination product	Node-sparing Radiotherapy Group
First-line treatmentPatients will receive 8 cycles of FOLFOX chemotherapy combined with bevacizumab, followed by maintenance therapy with bevacizumab and 5-fluorouracil (5-FU), administered every 2 weeks (Q2W).	Combination product	First-line therapy Group

Primary outcome

Objective Response Rate(ORR)
Time frame: From initiation of treatment until disease progression or death, whichever occurs first, assessed over a period of up to 36 months
Phase II: To evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and a PD-1 inhibitor can improve Objective Response Rate(ORR) in patients with metastatic pMMR/MSS colorectal cancer.
Progression-free survival (PFS)
Time frame: From initiation of treatment until disease progression or death, whichever occurs first, assessed over a period of up to 36 months
Phase III: To evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and a PD-1 inhibitor can improve progression-free survival (PFS) in patients with metastatic pMMR/MSS colorectal cancer.

5 secondary outcomes

Duration of response
Time frame: From the first documented occurrence of complete response (CR) or partial response (PR) to the first documented disease progression (per RECIST v1.1) or death from any cause, whichever occurs first, assessed over a period of up to 36 months
Disease control rate
Time frame: From treatment start to the end of study at 3 years
Overall survival (OS) rate
Time frame: From treatment start to the end of study at 3 years
Treatment related adverse effect
Time frame: From treatment start to 30 days after the end of treatment
Time to response (TTR)
Time frame: From randomization to the first documented occurrence of complete response (CR) or partial response (PR), assessed over a period of up to 36 months

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 7 Aug 2025.
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.

Yanxin Luo, M.D., Ph.D. contact

+86-20-38254221

luoyx25@mail.sysu.edu.cn

Yikan Cheng contact

15102033641

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 29 inclusion and 34 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 7 Aug 2025. 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Yanxin Luo, M.D., Ph.D. (+86-20-38254221, luoyx25@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate(ORR) (time frame: From initiation of treatment until disease progression or death, whichever occurs first, assessed over a period of up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06958419.

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 7 Aug 2025.