Neoadjuvant Moderately Hypofractionated Radiotherapy Combined with Chemotherapy and Immunotherapy for High-risk LARC

NCT06599827 | Not Yet Recruiting Phase 2

• 1 other identifier: B2024-271
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the effectiveness and safety of combining moderately hypofractionated radiotherapy with chemotherapy and anti-PD-1 antibodies as a neoadjuvant treatment for high-risk locally advanced rectal cancer.

Conditions

Rectal Cancer

Keywords

Moderately Hypofractionated Radiotherapy; Immunotherapy; Locally Advanced Rectal Adenocarcinoma; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• pathologic complete response (pCR)

  Proportion of patients in whom no cancer cells are found in resected rectal tissue and regional lymph nodes upon pathological evaluation.

  30-day

Secondary Outcomes (8)

• disease-free survival (DFS)

  3-year

• event-free survival (EFS)

  3-year

• objective response rate (ORR)

  3-month

• overall survival (OS)

  3-year

• adverse events

  3-year

Study Arms (1)

Experimental group

EXPERIMENTAL

This study examines combined radiotherapy, chemotherapy, and immunotherapy for high-risk locally advanced rectal cancer. After a week post-radiotherapy, patients start CapeOx chemotherapy with anti-PD-1 mAb. Surgery follows after 3 cycles of this regimen.

Radiation: moderately hypofractionated radiotherapy; Drug: chemotherapy; Drug: immunotherapy; Procedure: Total mesorectal excision (TME) surgery

Interventions

moderately hypofractionated radiotherapy RADIATION

35 Gy in 10 fractions to mesorectal and metastatic lymph nodes, and 30 Gy in 10 fractions to pelvic lymphatic drainage area, weekly over 5 days at 3-3.5 Gy/day.

Experimental group

chemotherapy DRUG

CapeOx-Capecitabine 1000 mg/m² orally twice daily (days 1-14, every 21 days) + Oxaliplatin 130 mg/m² IV (day 1, every 21 days).

Experimental group

immunotherapy DRUG

Serplulimab 300 mg IV infusion on day 1 every 21 days.

Experimental group

Total mesorectal excision (TME) surgery PROCEDURE

Total mesorectal excision (TME) surgery assessment post 3 cycles of chemotherapy and immunotherapy; eligible patients undergo TME surgery.

Experimental group

Eligibility Criteria

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

You may qualify if:

• Age ≥18 and ≤75 years.
• MRI-confirmed rectal adenocarcinoma with the lower edge of the lesion ≤10cm from the anal verge.
• Immunohistochemistry confirms proficiency in DNA mismatch repair (pMMR), or genetic testing confirms microsatellite instability-low (MSI-L) or microsatellite stable (MSS) status.
• Pelvic MRI showing one of the following high-risk factors: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph nodes.
• ECOG performance status of 0-1.
• No prior surgery, radiotherapy, chemotherapy, or targeted therapy.
• Tolerable to radiotherapy, chemotherapy, and immunotherapy with laboratory results: WBC ≥4.0 × 10\^9/L, platelets ≥100 × 10\^9/L, hemoglobin ≥80g/L, ALT \<2ULN, TB \<35μmol/L, Scr \<1.5ULN or creatinine clearance rate ≥50mL/min, TSH ≤ULN (if abnormal, consider T3 and T4 levels; if T3 and T4 are normal, patients can still be included).
• Voluntary participation with signed informed consent.

You may not qualify if:

• Distant metastases.
• Stage I or II rectal cancer not requiring neoadjuvant therapy.
• Severe cardiovascular, pulmonary, neurological, renal, gastrointestinal, or systemic diseases.
• Untreated chronic hepatitis B carrier with HBV DNA \>500 IU/ml, HCV RNA positive patients, except for inactive hepatitis B surface antigen carriers, stable hepatitis B (HBV DNA \<500 IU/ml), and cured hepatitis C patients.
• History of active autoimmune diseases or potential relapse of autoimmune diseases.
• Patients who received corticosteroids (equivalent to prednisone \>10mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration.
• History of thyroid dysfunction.
• Severe chronic or active infections requiring systemic antifungal or antiviral therapy, including tuberculosis.
• Known allergy or hypersensitivity to multiple drugs.
• History of pelvic radiation.
• History of inflammatory bowel disease.
• Unwillingness to participate or sign informed consent.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200030, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Drug Therapy; Immunotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy

Study Officials

• Jian Wang, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Genwen Chen, MD, PhD

CONTACT

86-021-64041990; chengenwen@fudan.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: SPONSOR

Model Details: Patients will receive CapeOx chemotherapy, anti-PD-1 mAb immunotherapy, and moderately hypofractionated radiotherapy.

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: September 19, 2024
• Study Start: September 20, 2024
• Primary Completion (Estimated): September 20, 2026
• Study Completion (Estimated): September 20, 2029
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)