Short-course Radiation (SCRT) Followed by 6 Cycles of Cadonilimab Plus MFOLFOX6 As Neoadjuvant Therapy for Patients with Locally Advanced Rectal Cancer (LARC): a Multicenter, Two-arm Parallel, Open-label, Randomised Phase III Trial (NeoCaCRT-III)

NCT06832917 | Not Yet Recruiting Phase 3

• 1 other identifier: Shenzhen CRC-005
• Study Type: interventional
• Target: 238
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if neoadjuvant short-course radiation (SCRT) followed by 6 cycles of cadonilimab plus mFOLFOX6 works to treat patients with locally advanced rectal cancer (LARC). It will also learn about the safety of the combined regimen. The main questions it aims to answer are: Does the neoadjuvant SCRT plus dual immunotherapy and chemotherapy can improve pathological complete response(pCR) rate? What medical problems do participants have when receiving chemotherapy plus cadonilimab compared to chemotherapy only? Participants will: Receiving cadonilimab plus mFOLFOX6 or mFOLFOX6 every 2 weeks for 3 months Visit the clinic once every 2 weeks for checkups and tests

Conditions

Rectal Cancer

Keywords

Mismatch repair-proficient (pMMR) or microsatellite stability(MSS); Locally advanced rectal cancer (LARC); Short course radiation (SCRT)

Outcome Measures

Primary Outcomes (1)

• 3-year disease free survival (3-y DFS)

  The survival rate of patients without disease recurrence or death due to the disease progression patients at 36 months.

  3-year

Secondary Outcomes (5)

• Pathological complete response rate

  Up to 6 months

• Overall Survival

  Up to 5 years

• Objective Response Rate

  Up to 6 months

• Clinical complete response rate

  Up to 36 months

• Incidence of adverse events

  Up to 36 months

Study Arms (2)

AK104 plus

EXPERIMENTAL

SCRT followed by AK104 plus chemotherapy

Drug: AK104 plus; Drug: Chemo only

Chemo only

OTHER

SCRT followed by chemotherapy

Drug: Chemo only

Interventions

AK104 plus DRUG

SCRT followed by 6 cycles of cadonilimab (AK104) plus mFOLFOX6 as neoadjuvant therapy for patients

AK104 plus

Chemo only DRUG

Short-course radiation (SCRT) followed by 6 cycles of mFOLFOX6 as neoadjuvant therapy for patients

AK104 plus; Chemo only

Eligibility Criteria

• Age: 18 Years - 79 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 yeas and ≤79 years. The gender is not limited. 2. Histopathology confirmed the diagnosis of rectal adenocarcinoma. 3. Patients with rectal cancer based on endoscopic ultrasound and / or pelvic MRI contrast + contrast, chest CT, head MRI or CT + contrast, or PET / CT, staging criteria per AJCC 8th edition cancer stage, cT 3-T4 / N + M0.
• \. At least 20 unstained sections of formalin-fixed paraffin-embedded tumor tissue sections, or fresh tumor tissue, can be provided for genomic and proteomic testing.
• \. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0- 1. 6. Adequate bone marrow and organ function meets the following criteria:
• Neutrophil count (ANC)≥1.5×l09/L
• Platelet (PLT) ≥80×109/L
• Hemoglobin (Hb) level ≥90 g/L
• Total bilirubin level≤1.5×ULN
• Alanine aminotransferase (ALT) level≤3×ULN
• Aspartate aminotransferase (AST) level ≤3×ULN
• International normalized value (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN
• Serum creatinine (Cr) level ≤1.5×ULN
• Creatinine clearance #50 ml/min (Calculated according to the Cockcroft-Gault formula)

You may not qualify if:

• \. Previous history of severe hypersensitivity to other monoclonal antibodies or any component of AK 104.
• \. Preoperative pathology was diagnosed as squamous cell carcinoma or neuroendocrine tumor 3. Within 5 years before enrollment for malignancies other than colorectal cancer with negligible risk of metastasis or death (e. g., expected 5-year OS\> 90%) and expected radical results after treatment (e. g., adequately treated cervical carcinoma in situ, basal or squamous cell skin carcinoma, localized prostate carcinoma for curative intent, ductal carcinoma in situ surgically treated with curative intent).
• \. Previous treatment against the PD-1 receptor or its ligand PD-L1 or the cytotoxic T lymphocyte-associated protein-4 (CTLA-4) receptor.
• \. History of autoimmune diseases, including but not limited to myasthenia gravis, myoitis, autoimmune hepatitis, series, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis related to antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, vasculitis, or glomerulnephritis; patients with autoimmune-related hypothyroidism were eligible for stable-dose thyroid hormone replacement therapy; patients with type 1 diabetes under control after a stable insulin regimen were eligible to participate in this study; 6. Receiving systemic immune stimulation drugs (including but not limited to interferon or IL-2) within 4 weeks prior to enrollment or within 5 half-lives of the drug (whichever is shorter); 7. Received systemic corticosteroids (\> 10 mg/d of prednisone equivalent) or other systemic immunosuppressive agents (including but not limited to prednisone, prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents \[anti-TNF\]) within 2 weeks prior to enrollment. Local, ocular, intra-articular, nasal, and inhaled corticosteroids are permittedt; 8. Patients requiring baseline and subsequent MRI tumor evaluation with previous allergic reactions to intravenous contrast agents may use preventive steroids.
• \. Allowing the use of inhaled corticosteroids for chronic obstructive pulmonary disease, corticosteroid hydrochloride (e. g., flurohydrocortisone) in patients with orthostatic hypotension, and low-dose corticosteroid maintenance for adrenal cortical insufficiency.
• \. Patients with previous allogeneic bone marrow transplantation or previous solid organ transplantation.
• \. Idiopathic pulmonary fibrosis, drug-induced pneumonia, mechanical pneumonia (i. e. bronchiolitis obliterans), history of idiopathic pneumonia or chest CT scan at screening showed evidence of active pneumonia.
• \. Any live vaccine (e. g., vaccine against infectious diseases, such as influenza vaccine, varicella vaccine, etc.) within 4 weeks (28 days) before enrollment.13 Active infections, including tuberculosis (clinical diagnosis including clinical history, physical examination and imaging findings, and TB tests performed per local medical practice), hepatitis B {known HBV surface antigen (HBsAg) positive and HBVDNA 1000 cps / ml}, hepatitis C or human immunodeficiency virus (HIV antibody positive).
• \. Patients with prior or cured HBV infection (defined as hepatitis B core antibody \[anti-HBc\] positive and HbsAg negative) were to be eligible to participate in the study only if HBVDNA was negative (HBVDNA˂ 1000 cps / ml).
• \. Patients with positive hepatitis C (HCV) antibody are not eligible for the study only if polymerase chain reaction shows negative HCVRNA.
• \. Clinically meaningful basic medicine, disease (e. g., dyspnea, pneumonia, pancreatitis, poorly controlled, poorly controlled diabetes, infection active or poorly controlled, or drug or alcohol abuse).
• \. Presence of severe neurological or psychiatric disorders, including dementia and epileptic seizures.
• \. He had an NCI-CTCAE grade 2 peripheral neuropathy. 18. Female patients during pregnancy or lactation. 19. Chronic bowel disease or short bowel syndrome. 20. Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. 21. Major cardiovascular diseases, such as New York Heart Association heart disease (grade II or higher), myocardial infarction within 3 months before randomization, unstable arrhythmia, or unstable angina pectoris.
• \. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \<50% must have an optimized stable medical regimen as determined by the treating physician, consulting a cardiologist if required.

Sponsors & Collaborators

• Wan He: lead

MeSH Terms

Conditions

Rectal Neoplasms

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

Study Officials

• WA He, Doctor

  Shenzhen Peolple's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wan He, Doctor

CONTACT

18823719462; 393322301@qq.com

Guixiang Liao, Doctor

CONTACT

18823719462; 393322301@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. He

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: February 18, 2025
• Study Start: March 31, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share