Neoadjuvant Therapy for Locally Advanced Low Rectal Cancer (SMARTi-RC01)

NCT07134101 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-SR-610
• Study Type: interventional
• Target: 138
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Conditions

Colorectal Cancer (Diagnosis)

Outcome Measures

Primary Outcomes (1)

• 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

  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

  From the end of neoadjuvant therapy through 3 years of follow-up.

• R0 Resection Rate confirmed by histopathology

  At the time of surgery.

• Disease-Free Survival (DFS) measured by imaging and clinical follow-up

  Up to 5 years after randomization.

• Overall Survival (OS) assessed by survival follow-up

  Time Frame: Up to 5 years after randomization.

• Objective Response Rate (ORR) assessed by RECIST v1.1

  During neoadjuvant therapy (baseline to pre-surgery evaluation).

Study Arms (2)

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.

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.

Drug: Serplulimab; Radiation: Short-Course Radioterapy; Drug: Chemotherapy (CAPOX or capecitabine)

Interventions

Serplulimab DRUG

Serplulimab 300 mg IV on Day 1

Also known as: Hanszhuo®

Control Arm; Experimental Arm

Bevacizumab DRUG

Bevacizumab 5 mg/kg IV on Day 1

Also known as: Zercepac®

Experimental Arm

Short-Course Radioterapy RADIATION

25 Gy in 5 fractions over 1 week

Control Arm; Experimental Arm

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

Control Arm; Experimental Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

MeSH Terms

Conditions

Colorectal Neoplasms; Disease

Interventions

Bevacizumab; Drug Therapy; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Xiaoke Di, Ph.D

CONTACT

8618761656786; dixiaoke@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Colorectal Cancer Center

Study Record Dates

• First Submitted: August 11, 2025
• First Posted: August 21, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2030
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share