SCRT-CAPEOX-Serplulimab for MSS/pMMR Rectal Cancer With Oligometastases

NCT06850103 | Recruiting Phase 2

• 1 other identifier: SCRT-CAP-Serp TriFire
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Background and Significance: Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths globally. Despite improved early screening rates, a significant proportion of newly diagnosed CRC patients present with synchronous metastases, predominantly liver metastases. The concept of oligometastases, introduced by Hellman and Weichselbaum in 1995, describes a transitional state between localized disease and widespread metastases, characterized by limited metastatic lesions (typically 1-5) confined to 1-2 organs. Current Treatment Landscape: The management of oligometastatic disease combines local therapeutic approaches (surgery, radiotherapy, radiofrequency ablation) with systemic treatments, aiming to achieve No Evidence of Disease (NED) status. The ESMO guidelines officially categorized metastatic CRC into oligometastatic and widespread metastatic states in 2016, emphasizing the importance of integrated local and systemic treatments for oligometastatic colorectal liver metastases (CRLM). Treatment Evolution and Challenges: While the EPOC study established CAPEOX neoadjuvant chemotherapy followed by R0 resection as the standard treatment for initially resectable CRLM, patients with synchronous rectal cancer oligometastases present unique challenges due to complex local anatomy and high local recurrence risks. Although various neoadjuvant approaches, including Total Neoadjuvant Therapy (TNT), have been studied, they have not demonstrated significant long-term survival benefits, primarily because distant metastases impact survival more significantly than local recurrence. Innovative Approach: Recent success with Immunotherapy-Based Total Neoadjuvant Therapy (iTNT) in microsatellite stable/proficient mismatch repair (MSS/pMMR) locally advanced rectal cancer has shown promising results. Short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy has demonstrated superior efficacy trends, attributed to radiation's immune-activating effects on both local and distant tumor microenvironments. Research Objective: This project aims to evaluate the effectiveness of iTNT combined with SCRT in MSS/pMMR rectal cancer patients with synchronous oligometastases. The novel approach integrates SCRT with CAPEOX chemotherapy and Serplulimab, potentially improving complete response rates, organ preservation opportunities, and overall treatment efficacy while reducing recurrence risks. This pioneering study represents the first investigation of iTNT in synchronous rectal cancer oligometastases, offering a potentially transformative treatment strategy for this challenging patient population. Research Innovation: The study uniquely combines SCRT, CAPEOX chemotherapy, and Serplulimab in a neoadjuvant setting for MSS/pMMR synchronous rectal cancer oligometastases, addressing an unmet clinical need and potentially establishing a new treatment paradigm in this field.

Conditions

Colorectal Carcinoma; Oligometastases; pMMR; MSS; iTNT

Outcome Measures

Primary Outcomes (1)

• 3-year PFS

  within 3 years from study enrollment.

Secondary Outcomes (4)

• No Evidence of Disease (NED) rate

  Within 3 months after surgery

• Primary tumor pathological complete response (pCR) rate

  After surgery

• 3-year local recurrence rate (LRR)

  within 3 years after primary treatment

• 5-year OS

  within 5 years from study enrollment.

Study Arms (1)

Experimental

EXPERIMENTAL

Patients in the experimental arm will receive short-course radiotherapy (SCRT) followed by 4 cycles of CAPEOX chemotherapy plus Serplulimab as neoadjuvant therapy, then undergo TME resection of the primary tumor and local treatment of metastatic lesions, followed by 4 additional cycles of CAPEOX plus Serplulimab as adjuvant therapy.

Radiation: short-course radiotherapy; Drug: CAPEOX/XELOX; Drug: Serplulimab; Procedure: surgery

Interventions

short-course radiotherapy RADIATION

Neoadjuvant short-course radiotherapy (SCRT) will be administered at a total dose of 25 Gy, delivered in 5 fractions of 5 Gy each.

Experimental

CAPEOX/XELOX DRUG

Capecitabine: 1000 mg/m² BID, D1-14, Q3W × 4 cycles Oxaliplatin: 130 mg/m² IV, D1, Q3W × 4 cycles

Experimental

Serplulimab DRUG

Serplulimab: 300 mg IV, D1, Q3W × 4 cycles

Experimental

surgery PROCEDURE

Primary tumor: Total Mesorectal Excision (TME) Metastatic lesions: Local therapeutic intervention

Experimental

Eligibility Criteria

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

You may qualify if:

• \- Has signed the written Informed Consent Form (ICF) and is able to comply with protocol-specified visits and procedures.
• Age between 18-75 years.
• Histologically confirmed primary rectal adenocarcinoma, with MRI showing tumor location within 10cm from the anal verge.
• Synchronous oligometastatic rectal cancer confirmed by comprehensive imaging evaluation (contrast-enhanced CT, contrast-enhanced MRI, PET-CT, etc.), with ≤2 metastatic sites and ≤5 total metastatic lesions.
• Microsatellite stability status confirmed as MSS (using the NCI-recommended 5 microsatellite markers: BAT25, BAT26, D5S346, D2S123, D17S250) or proficient mismatch repair (pMMR) status confirmed by immunohistochemistry showing positive nuclear expression of all 4 MMR proteins (MLH1, MSH2, MSH6, PMS2).
• At least one measurable lesion according to RECIST v1.1 criteria.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
• Adequate organ function and bone marrow reserve, defined as follows:
• Complete blood count:
• Absolute Neutrophil Count (ANC) ≥1.5×109/L Platelet count (PLT) ≥100×109/L Hemoglobin (HGB) ≥10.0g/dL
• Liver function:
• Total Bilirubin (TBIL) ≤1.5×Upper Limit of Normal (ULN) Alanine transaminase (ALT) and Aspartate aminotransferase (AST) ≤3×ULN Serum albumin (ALB) ≥35 g/L
• Renal function:
• Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min (calculated using Cockcroft-Gault formula \[see Appendix 3\] or standard 24-hour urine collection method) Urine protein by dipstick \<2+ For subjects with baseline urine protein ≥2+ by dipstick, 24-hour urine protein must be \<1g
• Coagulation:

You may not qualify if:

• \- More than 2 metastatic sites or more than 5 total metastatic lesions confirmed by imaging evaluation.
• Prior anti-tumor therapy for the study disease, including surgery, radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
• Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies, or any other drugs targeting T-cell co-stimulation or immune checkpoint pathways (e.g., OX40, CD137), or adoptive cell immunotherapy.
• Concurrent participation in another clinical trial, except for observational (non-interventional) studies or survival follow-up phase of interventional studies.
• Receipt of any investigational drug within 4 weeks prior to first dose of study drug.
• History of blood transfusion or use of G-CSF, GM-CSF, EPO, TPO, or IL-11 within 14 days prior to screening laboratory tests.
• Use of immunosuppressive medications within 4 weeks prior to first dose of study drug, excluding:
• Intranasal inhaled corticosteroids or local steroid injections Systemic corticosteroids at ≤10 mg/day prednisone equivalent Corticosteroids as premedication for allergic reactions (e.g., CT contrast) Traditional Chinese medicines with anti-tumor indications or immunomodulatory effects within 1 week prior to first dose Receipt of live or attenuated vaccines within 4 weeks prior to first dose or anticipated during the study period.
• Major surgery within 4 weeks prior to first dose (e.g., craniotomy, thoracotomy, or laparotomy), anticipated major surgery during treatment (excluding protocol-specified rectal cancer surgery), or presence of unhealed wounds, ulcers, or fractures.
• Known active or suspected autoimmune disease or history within past 2 years (exceptions: eczema, vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment in past 2 years; hypothyroidism requiring only hormone replacement; Type I diabetes requiring only insulin).
• Known history of primary immunodeficiency.
• Active tuberculosis, current anti-TB treatment, or anti-TB treatment within 1 year prior to first dose.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Known allergy to capecitabine, oxaliplatin, serplulimab, or other monoclonal antibody components.
• Clinically significant ascites, pleural effusion requiring intervention, or symptomatic pericardial effusion requiring drainage.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• Ningbo No.2 Hospital: collaborator
• Ningbo Medical Center Lihuili Hospital: collaborator
• Second Affiliated Hospital of Wenzhou Medical University: collaborator
• Ningbo No. 1 Hospital: collaborator
• Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University: collaborator
• The Affiliated People's Hospital of Ningbo University: collaborator

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

XELOX; Surgical Procedures, Operative

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

Central Study Contacts

Feng Ye

CONTACT

86-13858191208; yefeng-h1@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: February 27, 2025
• Study Start: April 22, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 1, 2032
• Last Updated: March 25, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)