XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for Locally Advanced, pMMR Rectal Cancer

XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for MRF-negative Locally Advanced, pMMR Rectal Cancer: a Randomised, Phase 2 Trial

This is a two-arm, open label, randomized phase II clinical study. The aim is to evaluate the safety and efficacy of Cadonilimab (a PD-1/CTLA-4 bispecific antibody) combined with XELOX regimen in pMMR locally advanced rectal cancer during the perioperative period. Eligible patients will receive either Cadonilimab plus XELOX or XELOX alone for 4 cycles before and 4 cycles after surgery. The primary endpoint is the pathological complete response rate.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer; MSS
• Intervention / Treatment: Drug: Cadonilimab; Drug: Oxaliplatin; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aiping Zhou, M.D.; Phone Number: 86-10-87788800; Email: zhouap1825@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
      • Contact: Aiping Zhou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or pathologically confirmed rectal adenocarcinoma located within 5 to 15cm from the anus with a stage of T3-4a or N+ according to the CT or endoscope
• Mesorectal fascia uninvolved
• Sign the informed consent form
• 18 years and older
• Mismatch repair proficient determined by immunohistochemistry
• No prior treatment
• Performance status: ECOG 0-1
• Good organ function:

Blood routine: hemoglobin ≥90g/L, neutrophil ≥1.5×10^9/L, platelet ≥100×10^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL; Ejection fraction at least 50% (or lower limit of normal) by echocardiogram

Exclusion Criteria:

• Other pathological category, such as squamous cancer
• Distant metastasis or peritoneum implantation
• Have received chemotherapy or radiotherapy in the past
• Known to have allergic reactions to any ingredients or excipients of experimental drugs
• Unable to swallow or under other circumstance which would drug absorption
• Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment
• Have received colorectal cancer surgery
• Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug
• Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months
• Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C
• Pregnant or nursing
• May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results
• There are other serious diseases that the researchers believe patients cannot be included in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadonilimab + XELOX; Oxaliplatin 130 mg/m2 iv and Cadonilimab 10mg/kg iv on day 1； Capecitabine 1000mg/m2 po bid on day 1 to 14； every 21 day as a cycle, 4 cycles before surgery and 4 cycles after surgery	Drug: Cadonilimab; 10mg/kg iv on day 1, every 21 day; Drug: Oxaliplatin; 130mg/m2 iv on day 1, every 21 day; Drug: Capecitabine; 1000mg/m2 po bid on day 1 to 14, every 21 day
Sham Comparator: XELOX; Oxaliplatin 130 mg/m2 iv on day 1； Capecitabine 1000mg/m2 po bid on day 1 to 14； every 21 day as a cycle, 4 cycles before surgery and 4 cycles after surgery	Drug: Oxaliplatin; 130mg/m2 iv on day 1, every 21 day; Drug: Capecitabine; 1000mg/m2 po bid on day 1 to 14, every 21 day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	the rate of pathological complete response	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR	the rate of major pathological response according to Becker-TRG	3 years
DFS	disease free survival	From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 3 years
OS	overall survival	From date of initiation of treatment to date of death, assessed up to 3 years

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Anticipated): March 1, 2025
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: April 1, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: NCC3627

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No