Clinical trial NCT05781958: Cadonilimab Combined With Gem/Cis as First Line Therapy in Patients With Advanced ICC
Official title: Cadonilimab Combined With Gemcitabine and Cisplatin as First Line Therapy in Patients With Advanced Intrahepatic Cholangiocarcinoma: A Single Center, Single Arm, Phase II Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Intrahepatic Cholangiocarcinoma
Keywords: cadonilimab (anti-PD-1/CTLA-4 bispecific antibody)
Lead sponsor: Eastern Hepatobiliary Surgery Hospital
Sponsor class: OTHER
First posted: 2023-03-23
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TOPAZ-1 phase III trail demonstrated that the addition of immune checkpoint inhibitor anti-PD-L1 antibody improved progression-free survival (PFS) and overall survival (OS) compared to Gem/Cis alone. Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in tumors. The goal of this clinical trial is to evaluated the efficacy and safety of cadonilimab combined with gemcitabine and cisplatin as first Line therapy in patients with advanced intrahepatic cholangiocarcinoma. Eligible participants will receive cadonilimab (up to 12 months) plus gemcitabine and cisplatin (for maximum of 6-8 cycles) until radiologic disease progression, unacceptable toxicity, or withdrawal from the study, whichever occurred first. The primary endpoint is objective response rate.


Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically diagnosed intrahepatic cholangiocarcinoma (ICC)
2. At least 1 measurable lesion (according to RECIST1.1)
3. Have not previously received any systemic treatment
4. Age 18-75 years old, both male and female
5. ECOG performance status score (PS score) 0-2 point
6. Adequate medullary hematopoiesis function: Neutrophils≥1.5\*10\^9/L; platelets≥100\*10\^9/L
7. Adequate renal function: creatinine clearance \> 60ml/min
8. Adequate hepatic function: Bilirubin ≤ 1.5 times the upper limit of normal
9. No cardiac insufficiency or chest pain (medically uncontrollable); no myocardial infarction in the 12 months prior to study initiation
10. Expectation survival time over 3 months
11. The patient must sign an informed consent form

Exclusion Criteria:

1. History of another primary malignancy
2. Brain metastases or spinal cord compression
3. Uncontrolled intercurrent illness
4. Have active or previously recorded autoimmune or inflammatory diseases (eg Rheumatoid arthritis, psoriasis, systemic lupus erythematosus, AIDS, etc)
5. Have received allogeneic organ transplantation
6. Control of concurrent complications, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, poorly controlled arrhythmia, active interstitial lung disease ( ILD), severe chronic gastrointestinal disorders associated with diarrhea symptoms, may limit compliance with the psychiatric/social conditions required by the trial, and substantially increase the risk of adverse events or affect the ability of patients to sign written consent forms
7. History of active primary immunodeficiency
8. Pregnant or lactating women
9. Severe or uncontrolled infections
10. Patients with history of severe neurological or psychiatric illness, including dementia or epilepsy;
11. Patients with drug abuse, medical, psychological or social conditions that may interfere with the study results or the assessment of the study results;
12. Patients are unsuitable for the enrollment according to investigator's judgement.

Primary outcomes:
measure: Objective response rate (ORR) per RECIST 1.1
timeFrame: Up to two years
Secondary outcomes:
measure: Progression free survival (PFS) per RECIST 1.1
timeFrame: Up to two years
measure: Desease control rate (DCR) per RECIST 1.1
timeFrame: Up to two years
measure: Overall survival (OS)
timeFrame: Up to two years
measure: 6mo PFS rate per RECIST 1.1
timeFrame: at 6 months
measure: adverse events
timeFrame: Up to two years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Eastern hepatobilliary surgery hospital
state: Shanghai
Study officials:
References: