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

NCT ID: NCT07134101

Last Updated: 2025-08-29

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2030-08-31

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arm

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.

Group Type: EXPERIMENTAL

Serplulimab

Intervention Type: DRUG

Serplulimab 300 mg IV on Day 1

Bevacizumab

Intervention Type: DRUG

Bevacizumab 5 mg/kg IV on Day 1

Short-Course Radioterapy

Intervention Type: RADIATION

25 Gy in 5 fractions over 1 week

Chemotherapy (CAPOX or capecitabine)

Intervention Type: 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

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.

Group Type: ACTIVE_COMPARATOR

Serplulimab

Intervention Type: DRUG

Serplulimab 300 mg IV on Day 1

Short-Course Radioterapy

Intervention Type: RADIATION

25 Gy in 5 fractions over 1 week

Chemotherapy (CAPOX or capecitabine)

Intervention Type: 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

Interventions

Serplulimab

Serplulimab 300 mg IV on Day 1

Intervention Type: DRUG

Bevacizumab

Bevacizumab 5 mg/kg IV on Day 1

Intervention Type: DRUG

Short-Course Radioterapy

25 Gy in 5 fractions over 1 week

Intervention Type: RADIATION

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

Intervention Type: DRUG

Other Intervention Names

Hanszhuo®; Zercepac®

Eligibility Criteria

Inclusion Criteria

Participants must meet all of the following criteria to be eligible for the study:

1. Age: 18 to 75 years old.

2. Diagnosis: Pathologically confirmed rectal adenocarcinoma with proficient mismatch repair (pMMR) / microsatellite stable (MSS) status, based on biopsy of the primary tumor.

3. Disease Stage: Untreated, preoperative clinical stage cT2-T4 and/or N+, M0 (AJCC 8th edition), unsuitable for initial local excision to achieve radical cure.

4. Tumor Location: Tumor within 8 cm from the anal verge, or assessed by surgeons as not suitable for immediate sphincter-preserving surgery.

5. Organ Preservation Intent: Strong desire for sphincter preservation and willingness to accept close surveillance for at least 2 years after chemoradiotherapy.

6. Surgical Candidacy: Agrees to undergo radical surgery and judged by surgeon to have no contraindication to surgery.

7. Cancer History: No concurrent multiple primary malignancies.

8. Measurable Lesions: At least one measurable or evaluable lesion according to RECIST v1.1 criteria.

9. Life Expectancy: ≥ 3 months.

10. Performance Status: ECOG performance status score of 0-1.

11. Compliance: Good compliance and willingness to sign written informed consent.

Exclusion Criteria

Participants will be excluded if any of the following conditions apply:

1. Molecular Subtype: Rectal cancer with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status.

2. Autoimmune Disease: Active, known, or suspected autoimmune disease.

3. Immunodeficiency: Known history of primary immunodeficiency.

4. Transplant History: History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

5. Pregnancy or Lactation: Pregnant or breastfeeding women.

6. Urgent Surgical Indications: Intestinal perforation, gastrointestinal bleeding, or other conditions requiring emergency surgery.

7. 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)

8. 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

9. Allergy: Known hypersensitivity to any component of the investigational drugs.

10. Other Clinical Trial Participation: Currently enrolled in another interventional drug clinical trial.

11. Other Conditions: Any other condition judged by the investigator to make the patient unsuitable for the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Fu Zan

Director of the Colorectal Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Xiaoke Di, Ph.D

Role: CONTACT

dixiaoke@njmu.edu.cn

8618761656786

Other Identifiers

2025-SR-610

Identifier Type: -

Identifier Source: org_study_id