Colorectal Cancer (Diagnosis)Phase 2SMARTi-RC01NCT07134101
Neoadjuvant Therapy for Locally Advanced Low Rectal Cancer (SMARTi-RC01)
A Phase 2 study testing Serplulimab, Bevacizumab and Short-Course Radioterapy in people with Colorectal Cancer (Diagnosis), run by The First Affiliated Hospital with Nanjing Medical University.
Trial summary
The goal of this clinical trial is to learn if combining serplulimab (PD-1 inhibitor) with bevacizumab and short-course total neoadjuvant therapy (TNT) works to treat locally advanced mid-to-low rectal cancer in adults. It will also learn about the safety of this combination. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer (Diagnosis)
- What is being tested?
- Serplulimab, Bevacizumab and Short-Course Radioterapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2025to 31 Aug 2030
- 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
- Participants must meet all of the following criteria to be eligible for the study:
- Age: 18 to 75 years old.
- Diagnosis: Pathologically confirmed rectal adenocarcinoma with proficient mismatch repair (pMMR) / microsatellite stable (MSS) status, based on biopsy of the primary tumor.
- Disease Stage: Untreated, preoperative clinical stage cT2-T4 and/or N+, M0 (AJCC 8th edition), unsuitable for initial local excision to achieve radical cure.
- Tumor Location: Tumor within 8 cm from the anal verge, or assessed by surgeons as not suitable for immediate sphincter-preserving surgery.
- Organ Preservation Intent: Strong desire for sphincter preservation and willingness to accept close surveillance for at least 2 years after chemoradiotherapy.
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- Surgical Candidacy: Agrees to undergo radical surgery and judged by surgeon to have no contraindication to surgery.
- Cancer History: No concurrent multiple primary malignancies.
- Measurable Lesions: At least one measurable or evaluable lesion according to RECIST v1.1 criteria.
- Life Expectancy: ≥ 3 months.
- Performance Status: ECOG performance status score of 0-1.
- Compliance: Good compliance and willingness to sign written informed consent.
Who cannot join
- Participants will be excluded if any of the following conditions apply:
- Molecular Subtype: Rectal cancer with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status.
- Autoimmune Disease: Active, known, or suspected autoimmune disease.
- Immunodeficiency: Known history of primary immunodeficiency.
- Transplant History: History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Pregnancy or Lactation: Pregnant or breastfeeding women.
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- Urgent Surgical Indications: Intestinal perforation, gastrointestinal bleeding, or other conditions requiring emergency surgery.
- Uncontrolled Comorbidities, including but not limited to:
- HIV infection (HIV antibody positive) Active or poorly controlled severe infection Active hepatitis Severe or uncontrolled systemic diseases (e.g., severe psychiatric or neurological disorders, epilepsy, dementia, unstable or decompensated respiratory, cardiovascular, hepatic, or renal disease, uncontrolled hypertension ≥ CTCAE Grade 2 despite medication) Active bleeding or recent thrombotic disease requiring therapeutic anticoagulation, or bleeding tendency, or coagulation abnormalities (INR > 1.5 × ULN, APTT > 1.5 × ULN)
- Laboratory Abnormalities at Baseline:
- Hemoglobin < 80 g/L Absolute neutrophil count (ANC) < 1.5 × 10⁹/L Platelets < 80 × 10⁹/L ALT or AST > 2.5 × ULN ALP > 2.5 × ULN Total bilirubin ≥ 1.5 × ULN Serum creatinine ≥ 1 × ULN
- Allergy: Known hypersensitivity to any component of the investigational drugs.
- Other Clinical Trial Participation: Currently enrolled in another interventional drug clinical trial.
- Other Conditions: Any other condition judged by the investigator to make the patient unsuitable for the study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Neoadjuvant Chemoradiotherapy Combined With Serplulimab With or Without Bevacizumab for Locally Advanced Rectal Cancer: A Single-Center, Open-Label, Phase II Randomized Trial
The goal of this clinical trial is to learn if combining serplulimab (PD-1 inhibitor) with bevacizumab and short-course total neoadjuvant therapy (TNT) works to treat locally advanced mid-to-low rectal cancer in adults. It will also learn about the safety of this combination.
The main questions it aims to answer are:
Read more
Does adding bevacizumab to serplulimab and TNT increase the complete remission rate (cCR + pCR) compared with serplulimab and TNT alone? What medical problems do participants have when receiving these treatments?
Researchers will compare:
Experimental group: serplulimab + bevacizumab + chemotherapy + short-course radiotherapy Control group: serplulimab + chemotherapy + short-course radiotherapy
Participants will:
Receive either the experimental or control regimen for about 4-5 months before surgery or a watch-and-wait approach if complete response is achieved Undergo treatment in cycles that include chemotherapy, immunotherapy (and bevacizumab if in the experimental group), and short-course radiotherapy Visit the clinic regularly for check-ups, blood tests, imaging, endoscopy, and to monitor side effects Be followed for up to 5 years after treatment to assess cancer control, organ preservation, and survival outcomes
- Conditions
- Colorectal Cancer (Diagnosis)
- Being tested
- Serplulimab, Bevacizumab, Short-Course Radioterapy, Chemotherapy (CAPOX or capecitabine)
- Medical subject headings
- Colorectal Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SerplulimabDrug
Also called Hanszhuo®
Serplulimab 300 mg IV on Day 1
BevacizumabDrug
Also called Zercepac®
Bevacizumab 5 mg/kg IV on Day 1
Short-Course RadioterapyRadiation
25 Gy in 5 fractions over 1 week
Chemotherapy (CAPOX or capecitabine)Drug
Capecitabine: 800 mg/m² orally, twice daily (BID), on Days 1-14 of each cycle Oxaliplatin: 130 mg/m² intravenous infusion, on Day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Experimental Arm Induction Phase (2 cycles, every 3 weeks) Chemotherapy: CAPOX (capecitabine + oxaliplatin) or capecitabine monotherapy Capecitabine: 800 mg/m² orally, twice daily (BID), on Days 1-14 of each cycle Oxaliplatin: 130 mg/m² intravenous infusion, on Day 1 of each cycle (if CAPOX) Immunotherapy: Serplulimab 300 mg IV on Day 1 of each cycle Anti-angiogenic therapy: Bevacizumab 5 mg/kg IV on Day 1 of each cycle Radiotherapy: Short-course radiotherapy, 25 Gy in 5 fractions over 1 week Consolidation Phase 2 cycles of CAPOX or capecitabine + serplulimab + bevacizumab Followed by 2 cycles of CAPOX or capecitabine + serplulimab (no bevacizumab) Post-treatment After completion of neoadjuvant treatment, patients will undergo total mesorectal excision (TME) surgery or follow a Watch-and-Wait strategy if a clinical complete response (cCR) is achieved. Receives: Drug: Serplulimab; Drug: Bevacizumab; Radiation: Short-Course Radioterapy; Drug: Chemotherapy (CAPOX or capecitabine) |
| Control Arm | Active comparator | Control Arm Induction Phase (2 cycles, every 3 weeks) Chemotherapy: CAPOX (capecitabine + oxaliplatin) or capecitabine monotherapy Capecitabine: 800 mg/m² orally, twice daily (BID), on Days 1-14 of each cycle Oxaliplatin: 130 mg/m² intravenous infusion, on Day 1 of each cycle (if CAPOX) Immunotherapy: Serplulimab 300 mg IV on Day 1 of each cycle Radiotherapy: Short-course radiotherapy, 25 Gy in 5 fractions over 1 week Consolidation Phase 4 cycles of CAPOX or capecitabine + serplulimab Post-treatment After completion of neoadjuvant treatment, patients will undergo total mesorectal excision (TME) surgery or follow a Watch-and-Wait strategy if a clinical complete response (cCR) is achieved. Receives: Drug: Serplulimab; Radiation: Short-Course Radioterapy; Drug: Chemotherapy (CAPOX or capecitabine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR) Rate assessed by pathology, MRI, endoscopy, and clinical examination
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
Measured: At the time of surgery for pCR, and at 1 year after achieving cCR for sustained cCR
Secondary outcomes (7)
Organ Preservation Rate (OPR) assessed by MRI, endoscopy, and clinical examination
Definition: The proportion of participants who achieve organ preservation, defined as avoiding radical rectal resection (TME) without evidence of local tumor recurrence during follow-up.
Assessment Method: Clinical examination, endoscopy, and MRI.
Measured: From the end of neoadjuvant therapy through 3 years of follow-up.
R0 Resection Rate confirmed by histopathology
Definition: The proportion of participants who undergo surgical resection with negative microscopic margins (no tumor cells at the resection margin).
Assessment Method: Pathology review of surgical specimens.
Measured: At the time of surgery.
Disease-Free Survival (DFS) measured by imaging and clinical follow-up
Definition: Time from randomization to documented disease recurrence (local or distant) or death from any cause, whichever occurs first.
Assessment Method: Imaging, endoscopic examination, clinical records.
Measured: Up to 5 years after randomization.
Overall Survival (OS) assessed by survival follow-up
Definition: Time from randomization to death from any cause. Assessment Method: Survival status by follow-up visits, phone calls, or registry data.
Measured: Time Frame: Up to 5 years after randomization.
Objective Response Rate (ORR) assessed by RECIST v1.1
Definition: The proportion of participants achieving a complete response (CR) or partial response (PR) according to RECIST v1.1 during neoadjuvant therapy.
Assessment Method: MRI, CT scans, and clinical examination.
Measured: During neoadjuvant therapy (baseline to pre-surgery evaluation).
Disease Control Rate (DCR) assessed by RECIST v1.1
Definition: The proportion of participants achieving CR, PR, or stable disease (SD) as per RECIST v1.1 during neoadjuvant therapy.
Assessment Method: MRI, CT scans, and clinical examination.
Measured: During neoadjuvant therapy (baseline to pre-surgery evaluation).
Safety Outcomes assessed by NCI-CTCAE v5.0
Definition: Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI-CTCAE v5.0;
Measured: From first dose to 90 days after last dose of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2025
- Study start1 Sep 2025 (estimated)
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer (Diagnosis)Studies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical 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
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fu Zan, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07134101
- Sponsor's protocol ID
- 2025-SR-610
- Acronym
- SMARTi-RC01
- Status last verified
- Aug 2025
- First submitted
- 11 Aug 2025
- Last updated
- 29 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- 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 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Chemoradiotherapy Combined With Serplulimab With or Without Bevacizumab for Locally Advanced Rectal Cancer: A Single-Center, Open-Label, Phase II Randomized Trial
- ClinicalTrials.gov ID
- NCT07134101
- Acronym / sponsor ID
- SMARTi-RC01 / 2025-SR-610
- Conditions
- Colorectal Cancer (Diagnosis)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2030 (estimated)
- First posted
- 21 Aug 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 learn if combining serplulimab (PD-1 inhibitor) with bevacizumab and short-course total neoadjuvant therapy (TNT) works to treat locally advanced mid-to-low rectal cancer in adults. It will also learn about the safety of this combination.
The main questions it aims to answer are:
Does adding bevacizumab to serplulimab and TNT increase the complete remission rate (cCR + pCR) compared with serplulimab and TNT alone? What medical problems do participants have when receiving these treatments?
Researchers will compare:
Experimental group: serplulimab + bevacizumab + chemotherapy + short-course radiotherapy Control group: serplulimab + chemotherapy + short-course radiotherapy
Participants will:
Receive either the experimental or control regimen for about 4-5 months before surgery or a watch-and-wait approach if complete response is achieved Undergo treatment in cycles that include chemotherapy, immunotherapy (and bevacizumab if in the experimental group), and short-course radiotherapy Visit the clinic regularly for check-ups, blood tests, imaging, endoscopy, and to monitor side effects Be followed for up to 5 years after treatment to assess cancer control, organ preservation, and survival outcomes
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: Serplulimab, Drug: Bevacizumab, Radiation: Short-Course Radioterapy, Drug: Chemotherapy (CAPOX or capecitabine)Experimental Arm Induction Phase (2 cycles, every 3 weeks) Chemotherapy: CAPOX (capecitabine + oxaliplatin) or capecitabine monotherapy Capecitabine: 800 mg/m² orally, twice daily (BID), on Days 1-14 of each cycle Oxaliplatin: 130 mg/m² intravenous infusion, on Day 1 of each cycle (if CAPOX) Immunotherapy: Serplulimab 300 mg IV on Day 1 of each cycle Anti-angiogenic therapy: Bevacizumab 5 mg/kg IV on Day 1 of each cycle Radiotherapy: Short-course radiotherapy, 25 Gy in 5 fractions over 1 week Consolidation Phase 2 cycles of CAPOX or capecitabine + serplulimab + bevacizumab Followed by 2 cycles of CAPOX or capecitabine + serplulimab (no bevacizumab) Post-treatment After completion of neoadjuvant treatment, patients will undergo total mesorectal excision (TME) surgery or follow a Watch-and-Wait strategy if a clinical complete response (cCR) is achieved. |
| Control Arm | Active comparator | Drug: Serplulimab, Radiation: Short-Course Radioterapy, Drug: Chemotherapy (CAPOX or capecitabine)Control Arm Induction Phase (2 cycles, every 3 weeks) Chemotherapy: CAPOX (capecitabine + oxaliplatin) or capecitabine monotherapy Capecitabine: 800 mg/m² orally, twice daily (BID), on Days 1-14 of each cycle Oxaliplatin: 130 mg/m² intravenous infusion, on Day 1 of each cycle (if CAPOX) Immunotherapy: Serplulimab 300 mg IV on Day 1 of each cycle Radiotherapy: Short-course radiotherapy, 25 Gy in 5 fractions over 1 week Consolidation Phase 4 cycles of CAPOX or capecitabine + serplulimab Post-treatment After completion of neoadjuvant treatment, patients will undergo total mesorectal excision (TME) surgery or follow a Watch-and-Wait strategy if a clinical complete response (cCR) is achieved. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age: 18 to 75 years old.
- Diagnosis: Pathologically confirmed rectal adenocarcinoma with proficient mismatch repair (pMMR) / microsatellite stable (MSS) status, based on biopsy of the primary tumor.
- Disease Stage: Untreated, preoperative clinical stage cT2-T4 and/or N+, M0 (AJCC 8th edition), unsuitable for initial local excision to achieve radical cure.
- Tumor Location: Tumor within 8 cm from the anal verge, or assessed by surgeons as not suitable for immediate sphincter-preserving surgery.
- Organ Preservation Intent: Strong desire for sphincter preservation and willingness to accept close surveillance for at least 2 years after chemoradiotherapy.
Key exclusion criteria (14 listed)
- Molecular Subtype: Rectal cancer with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status.
- Autoimmune Disease: Active, known, or suspected autoimmune disease.
- Immunodeficiency: Known history of primary immunodeficiency.
- Transplant History: History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- Pregnancy or Lactation: Pregnant or breastfeeding women.
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 |
|---|---|---|
| SerplulimabAlso: Hanszhuo®Serplulimab 300 mg IV on Day 1 | Drug | Control Arm, Experimental Arm |
| BevacizumabAlso: Zercepac®Bevacizumab 5 mg/kg IV on Day 1 | Drug | Experimental Arm |
| Short-Course Radioterapy25 Gy in 5 fractions over 1 week | Radiation | Control Arm, Experimental Arm |
| Chemotherapy (CAPOX or capecitabine)Capecitabine: 800 mg/m² orally, twice daily (BID), on Days 1-14 of each cycle Oxaliplatin: 130 mg/m² intravenous infusion, on Day 1 of each cycle | Drug | Control Arm, Experimental Arm |
Primary outcome
Complete Remission (CR) Rate assessed by pathology, MRI, endoscopy, and clinical examination
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
7 secondary outcomes
Organ Preservation Rate (OPR) assessed by MRI, endoscopy, and clinical examination
Time frame: From the end of neoadjuvant therapy through 3 years of follow-up.
R0 Resection Rate confirmed by histopathology
Time frame: At the time of surgery.
Disease-Free Survival (DFS) measured by imaging and clinical follow-up
Time frame: Up to 5 years after randomization.
Overall Survival (OS) assessed by survival follow-up
Time frame: Time Frame: Up to 5 years after randomization.
Objective Response Rate (ORR) assessed by RECIST v1.1
Time frame: During neoadjuvant therapy (baseline to pre-surgery evaluation).
Disease Control Rate (DCR) assessed by RECIST v1.1
Time frame: During neoadjuvant therapy (baseline to pre-surgery evaluation).
Safety Outcomes assessed by NCI-CTCAE v5.0
Time frame: From first dose to 90 days after last dose of study treatment.
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 29 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Serplulimab, Bevacizumab and Short-Course Radioterapy in people with Colorectal Cancer (Diagnosis), run by The First Affiliated Hospital with Nanjing Medical University.
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 12 inclusion and 14 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: opening soon, as of the sponsor's last update on 29 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
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 Xiaoke Di, Ph.D (8618761656786, dixiaoke@njmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission (CR) Rate assessed by pathology, MRI, endoscopy, and clinical examination (time frame: At the time of surgery for pCR, and at 1 year after achieving cCR for sustained cCR). 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 29 Aug 2025.