Rectal CancerPhase 2NCT06923345
Modified Long-Course Radiotherapy Followed by Chemotherapy and PD-1 Inhibitor for MSS/pMMR High-risk Mid/Low LARC (MODIFI-RC-I)
A Phase 2 study testing Reduced CTV and Conventional CTV in people with Rectal Cancer and Neoadjuvant Therapies, run by Sixth Affiliated Hospital, Sun Yat-sen University at 1 site in China.
Trial summary
The goal of this clinical trial is to evaluate whether a total neoadjuvant therapy (TNT) regimen combining long-course chemoradiotherapy, sequential chemotherapy, and PD-1 inhibitor can improve response rates, enhance tolerability, and improve prognosis in patients with locally advanced, microsatellite-stable (MSS)… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer, Neoadjuvant Therapies, Immune Checkpoint Therapy
- What is being tested?
- Reduced CTV and Conventional CTV
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 31 Mar 2025to 31 Dec 2028
- Phase
- Phase 2
- 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 enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Expected survival of more than 2 years.
- Histologically confirmed rectal adenocarcinoma.
- Tumor biopsy immunohistochemistry indicating pMMR (MSH1, MSH2, MSH6, and PMS2 all positive) or genetic testing confirming MSS.
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- According to the 8th edition of the AJCC TNM classification, high-resolution MRI ± endorectal ultrasound confirms clinical staging as cT3-4NanyM0 or cTxN+M0 (stage II-III rectal cancer). MRI confirms the tumor is located below the peritoneal reflection without lateral lymph node metastasis.
- Before study enrollment, a responsible surgical attending physician must evaluate the patient's medical history to confirm eligibility for R0 resection with curative intent.
- No prior systemic or local anti-tumor treatment for rectal cancer, including radiotherapy, chemotherapy, immunotherapy, biologics, or small-molecule targeted therapy.
- Willing to provide tumor tissue and peripheral blood samples for research purposes during screening and throughout the study.
- Adequate organ function:
- Hematology (without recent blood transfusions or growth factor support within 7 days before treatment):
- Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L (1,500/mm³)
- Platelet count ≥ 100 × 10⁹/L (100,000/mm³)
- Hemoglobin ≥ 90 g/L
- Renal function:
- Estimated creatinine clearance (CrCl) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
- Urine protein < 2+ or 24-hour urine protein quantification < 1.0 g
- Liver function:
- Total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN)
- AST and ALT ≤ 2.5 × ULN
- Serum albumin (ALB) ≥ 28 g/L
- Coagulation function:
- o INR and APTT ≤ 1.5 × ULN
- Cardiac function:
- o Left ventricular ejection fraction (LVEF) ≥ 50%
- Female participants of childbearing potential must have a negative urine or serum pregnancy test within 3 days before starting study treatment. If a urine pregnancy test result is unclear, a confirmatory serum pregnancy test must be conducted. Participants with childbearing potential who engage in sexual activity with non-sterilized male partners must use highly effective contraception from screening until 120 days after the last dose of study treatment. The use of periodic abstinence and fertility awareness methods is not considered acceptable contraception.
- Definition of females of childbearing potential (FCBP): Women who have not undergone surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or total hysterectomy) or who have not been naturally postmenopausal for at least 12 consecutive months (confirmed by FSH levels within the postmenopausal range).
- Highly effective contraception methods: Must have a failure rate of <1% per year when used consistently and correctly. In addition to barrier methods, FCBP must use an additional hormonal contraceptive method (e.g., oral contraceptives).
- Participants must be willing and able to comply with study visit schedules, treatment plans, laboratory tests, and other study-related requirements.
Who cannot join
- Presence of suspected metastatic lesions or locally advanced unresectable disease, regardless of disease stage.
- Diagnosis of other malignancies within the past five years, except for patients with malignancies cured through local treatment (e.g., basal or squamous cell skin cancer, superficial bladder cancer, ductal carcinoma in situ of the breast).
- Concurrent enrollment in another clinical study, unless it is an observational, non-interventional study or a follow-up phase of an interventional study.
- Presence of intestinal obstruction, perforation, or bleeding requiring emergency surgery.
- Multiple primary rectal cancers.
- History of pelvic or abdominal radiotherapy.
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- Inability to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption.
- Prior systemic or local anti-tumor treatment for locally advanced rectal cancer, including radical surgery, chemotherapy, radiotherapy, immunotherapy (e.g., immune checkpoint inhibitors, immune cell therapy), biological agents, or targeted therapy.
- Use of nonspecific immunomodulatory treatment (e.g., interleukins, interferons, thymosin, TNF) within two weeks before study treatment (excluding IL-11 for thrombocytopenia); use of traditional Chinese medicine with anti-tumor indications within one week before study treatment.
- Active autoimmune disease requiring systemic treatment in the past two years, except for replacement therapy (e.g., thyroid hormone, insulin, corticosteroids for adrenal/pituitary insufficiency).
- History of non-infectious pneumonitis requiring systemic glucocorticoid therapy or interstitial lung disease.
- History of severe bleeding tendency, coagulopathy, or long-term anticoagulation therapy (e.g., atrial fibrillation with CHADS2 score ≥2).
- Uncontrolled comorbidities, including but not limited to decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease, or psychiatric/social conditions limiting compliance.
- History of myocarditis, cardiomyopathy, malignant arrhythmias; hospitalization for unstable angina, congestive heart failure, or vascular diseases (e.g., aortic aneurysm requiring surgery) within 12 months before study treatment.
- History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea).
- Severe infection within four weeks before study treatment, including sepsis or severe pneumonia requiring hospitalization; active infection requiring systemic therapy within ten days before study treatment (excluding antiviral therapy for HBV or HCV).
- Major surgery or severe trauma within 30 days before study treatment; minor surgery (excluding peripheral venous catheterization) within three days before study treatment.
- Immunodeficiency history, positive HIV test, or long-term use of systemic corticosteroids or immunosuppressants.
- Active tuberculosis or suspected TB requiring clinical exclusion; known active syphilis infection.
- History of allogeneic organ or hematopoietic stem cell transplantation.
- Untreated active HBV infection (HBsAg-positive with HBV-DNA > 1000 copies/ml or 200 IU/ml); active HCV infection (HCV antibody-positive with detectable HCV-RNA).
- Live vaccine administration within 30 days before study treatment or planned during the study period.
- Known hypersensitivity to any study drug component or history of severe hypersensitivity reactions to monoclonal antibodies.
- History of psychiatric disorders, substance abuse, alcohol dependence, or drug addiction.
- Pregnant or breastfeeding women.
- Any disease, treatment, or laboratory abnormality that may confound study results, interfere with full study participation, or is not in the participant's best interest.
- Non-malignant or tumor-related systemic diseases or symptoms causing high medical risk or uncertainty in survival assessment.
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
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510655
Qian Wu, +86-020-38379764, zslyllb@mail.sysu.edu.cn
About this study
Official title: Modified Long-Course Radiotherapy (Reduced vs. Conventional CTV), Sequential Chemotherapy and PD-1 Inhibitor in Locally Advanced, MSS, Mid-Low Rectal Cancer: An Open-Label, Two-Arm, Randomized, Prospective Phase II Clinical Trial (MODIFI-RC-I)
The goal of this clinical trial is to evaluate whether a total neoadjuvant therapy (TNT) regimen combining long-course chemoradiotherapy, sequential chemotherapy, and PD-1 inhibitor can improve response rates, enhance tolerability, and improve prognosis in patients with locally advanced, microsatellite-stable (MSS) rectal cancer.
The main questions it aims to answer are:
Read more
Does this TNT approach improve complete response (CR) rates?
How does selective reduction of clinical target volume (CTV) to S2/S3 level compare with conventional CTV irradiation in terms of efficacy and safety?
Researchers will compare a selective CTV reduction group and a conventional CTV irradiation group to assess differences in treatment outcomes, including complete response, tumor regression grading (TRG), organ preservation, R0 resection rates, and long-term survival.
Participants will:
Receive long-course chemoradiotherapy with either conventional or reduced CTV irradiation.
Undergo sequential chemotherapy.
Receive PD-1 inhibitor treatment.
Be monitored for safety, tumor regression, and long-term survival outcomes.
- Being tested
- Reduced CTV, Conventional CTV
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced CTVCombination product
Long-course radiotherapy with selective CTV reduction (lower to S2/S3 level) + CAPOX + PD-1 inhibitor.
After treatment, patients will undergo TME surgery or a watch-and-wait approach, depending on response.
Conventional CTVCombination product
Long-course radiotherapy with conventional CTV irradiation + CAPOX + PD-1 inhibitor.
After treatment, patients will undergo TME surgery or a watch-and-wait approach, depending on response.
| Study group | Role | What they receive |
|---|---|---|
| Reduced CTV | Experimental | Patients will receive long-course radiotherapy with selective reduced CTV irradiation, concurrently with 3 cycles of CAPOX chemotherapy and PD-1 inhibitor. After radiotherapy, they will receive an additional 3 cycles of CAPOX chemotherapy and PD-1 inhibitor, followed by either total mesorectal excision (TME) surgery or watch-and-wait observation. Receives: Combination Product: Reduced CTV |
| Conventional CTV | Experimental | Patients will receive long-course radiotherapy with conventional CTV irradiation, concurrently with 3 cycles of CAPOX chemotherapy and PD-1 inhibitor. After radiotherapy, they will receive an additional 3 cycles of CAPOX chemotherapy and PD-1 inhibitor, followed by either total mesorectal excision (TME) surgery or watch-and-wait observation. Receives: Combination Product: Conventional CTV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response (CR) rate
Evaluate whether total neoadjuvant therapy (TNT) with long-course chemoradiotherapy (selective vs. conventional CTV), sequential CAPOX chemotherapy, and PD-1 inhibitor improves the complete response (CR) rate in locally advanced MSS rectal cancer.
Measured: From enrollment to 2 weeks after finishing TNT
Secondary outcomes (9)
Tumor regression grade (TRG)
Measured: From enrollment to 2 weeks after finishing TNT
Tumor downstaging rate
Measured: From enrollment to 2 weeks after finishing TNT
Watch-and-wait rate
Measured: From enrollment to 2 weeks after finishing TNT
Sphincter preservation rate
Measured: From date of randomization until the date of surgery or the date of watch-and-wait for CR patients
R0 resection rate
Measured: From date of randomization until the date of surgery or the date of watch-and-wait for CR patients
3-year event-free survival (EFS) rate
Measured: From enrollment to 3 years after finishing Surgery
3-year distant metastasis rate
Measured: From enrollment to 3 years after finishing Surgery
3-year local recurrence rate
Measured: From enrollment to 3 years after finishing Surgery
3-year overall survival (OS) rate
Measured: From enrollment to 3 years after finishing Surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2025
- Study start31 Mar 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 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.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Select-a-winner design
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanxin Luo,MD, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06923345
- Sponsor's protocol ID
- 2025ZSLYEC-147
- Status last verified
- Apr 2025
- First submitted
- 1 Apr 2025
- Last updated
- 18 Apr 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 18 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modified Long-Course Radiotherapy (Reduced vs. Conventional CTV), Sequential Chemotherapy and PD-1 Inhibitor in Locally Advanced, MSS, Mid-Low Rectal Cancer: An Open-Label, Two-Arm, Randomized, Prospective Phase II Clinical Trial (MODIFI-RC-I)
- ClinicalTrials.gov ID
- NCT06923345
- Acronym / sponsor ID
- 2025ZSLYEC-147
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Sixth Affiliated Hospital, Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 31 Mar 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 11 Apr 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.
The goal of this clinical trial is to evaluate whether a total neoadjuvant therapy (TNT) regimen combining long-course chemoradiotherapy, sequential chemotherapy, and PD-1 inhibitor can improve response rates, enhance tolerability, and improve prognosis in patients with locally advanced, microsatellite-stable (MSS) rectal cancer.
The main questions it aims to answer are:
Does this TNT approach improve complete response (CR) rates?
How does selective reduction of clinical target volume (CTV) to S2/S3 level compare with conventional CTV irradiation in terms of efficacy and safety?
Researchers will compare a selective CTV reduction group and a conventional CTV irradiation group to assess differences in treatment outcomes, including complete response, tumor regression grading (TRG), organ preservation, R0 resection rates, and long-term survival.
Participants will:
Receive long-course chemoradiotherapy with either conventional or reduced CTV irradiation.
Undergo sequential chemotherapy.
Receive PD-1 inhibitor treatment.
Be monitored for safety, tumor regression, and long-term survival outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Select-a-winner design
| Arm | Type | Receives |
|---|---|---|
| Reduced CTV | Experimental | Combination Product: Reduced CTVPatients will receive long-course radiotherapy with selective reduced CTV irradiation, concurrently with 3 cycles of CAPOX chemotherapy and PD-1 inhibitor. After radiotherapy, they will receive an additional 3 cycles of CAPOX chemotherapy and PD-1 inhibitor, followed by either total mesorectal excision (TME) surgery or watch-and-wait observation. |
| Conventional CTV | Experimental | Combination Product: Conventional CTVPatients will receive long-course radiotherapy with conventional CTV irradiation, concurrently with 3 cycles of CAPOX chemotherapy and PD-1 inhibitor. After radiotherapy, they will receive an additional 3 cycles of CAPOX chemotherapy and PD-1 inhibitor, followed by either total mesorectal excision (TME) surgery or watch-and-wait observation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Voluntarily signs a written informed consent form.
- Aged between 18 and 75 years at enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Expected survival of more than 2 years.
- Histologically confirmed rectal adenocarcinoma.
Key exclusion criteria (27 listed)
- Presence of suspected metastatic lesions or locally advanced unresectable disease, regardless of disease stage.
- Diagnosis of other malignancies within the past five years, except for patients with malignancies cured through local treatment (e.g., basal or squamous cell skin cancer, superficial bladder cancer, ductal carcinoma in situ of the breast).
- Concurrent enrollment in another clinical study, unless it is an observational, non-interventional study or a follow-up phase of an interventional study.
- Presence of intestinal obstruction, perforation, or bleeding requiring emergency surgery.
- Multiple primary rectal cancers.
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 |
|---|---|---|
| Reduced CTVLong-course radiotherapy with selective CTV reduction (lower to S2/S3 level) + CAPOX + PD-1 inhibitor. After treatment, patients will undergo TME surgery or a watch-and-wait approach, depending on response. | Combination product | Reduced CTV |
| Conventional CTVLong-course radiotherapy with conventional CTV irradiation + CAPOX + PD-1 inhibitor. After treatment, patients will undergo TME surgery or a watch-and-wait approach, depending on response. | Combination product | Conventional CTV |
Primary outcome
Complete response (CR) rate
Time frame: From enrollment to 2 weeks after finishing TNT
Evaluate whether total neoadjuvant therapy (TNT) with long-course chemoradiotherapy (selective vs. conventional CTV), sequential CAPOX chemotherapy, and PD-1 inhibitor improves the complete response (CR) rate in locally advanced MSS rectal cancer.
9 secondary outcomes
Tumor regression grade (TRG)
Time frame: From enrollment to 2 weeks after finishing TNT
Tumor downstaging rate
Time frame: From enrollment to 2 weeks after finishing TNT
Watch-and-wait rate
Time frame: From enrollment to 2 weeks after finishing TNT
Sphincter preservation rate
Time frame: From date of randomization until the date of surgery or the date of watch-and-wait for CR patients
R0 resection rate
Time frame: From date of randomization until the date of surgery or the date of watch-and-wait for CR patients
3-year event-free survival (EFS) rate
Time frame: From enrollment to 3 years after finishing Surgery
3-year distant metastasis rate
Time frame: From enrollment to 3 years after finishing Surgery
3-year local recurrence rate
Time frame: From enrollment to 3 years after finishing Surgery
3-year overall survival (OS) rate
Time frame: From enrollment to 3 years after finishing Surgery
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 18 Apr 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Reduced CTV and Conventional CTV in people with Rectal Cancer and Neoadjuvant Therapies, run by Sixth Affiliated Hospital, Sun Yat-sen University 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 30 inclusion and 27 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 18 Apr 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 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.
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. (+86-13826190263, 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?
Complete response (CR) rate (time frame: From enrollment to 2 weeks after finishing TNT). 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 18 Apr 2025.