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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 2

Conditions: MSS; Rectal Cancer

Treatments: Drug: Capecitabine; Drug: Cadonilimab; Drug: Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT05815303

NCC3627

Details and patient eligibility

About

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.

Enrollment: 92 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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92 participants in 2 patient groups

Cadonilimab + XELOX

Experimental group

Description:

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

Treatment:

Drug: Oxaliplatin

Drug: Cadonilimab

Drug: Capecitabine

XELOX

Sham Comparator group

Description:

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

Treatment:

Drug: Oxaliplatin

Drug: Capecitabine