Clinical trial NCT05815303: XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for Locally Advanced, pMMR Rectal Cancer
Official title: XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for MRF-negative Locally Advanced, pMMR Rectal Cancer: a Randomised, Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
MSS
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2023-04-18
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: pCR
timeFrame: 3 years
Secondary outcomes:
measure: MPR
timeFrame: 3 years
measure: DFS
timeFrame: From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 3 years
measure: OS
timeFrame: From date of initiation of treatment to date of death, assessed up to 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
Study officials:
References: