Cadonilimab Combined With Gem/Cis as First Line Therapy in Patients With Advanced ICC

Intrahepatic Cholangiocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05781958
• Other study ID #: EHBHKY2022-H039-P001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 24, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: October 2023
• Source: Eastern Hepatobiliary Surgery Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Intrahepatic Cholangiocarcinoma

Intervention

Drug:
• Cadonilimab+Gem/Cis
Cadonilimab (500mg, iv, Q3W, Day1) with gemcitabine(1000mg/m^2, iv, Q3W, Day1and Day8) plus cisplatin(25mg/m^2, iv, Q3W, Day1and Day8) up to 8 cycles followed by cadonilimab (500mg, iv, Q3W, Day1) plus capecitabine(1000 mg/m^2 orally according to Body Surface Area (BSA),BID,Q3W,on Days 1-14)as maintenance therapy until disease progression or other discontinuation criteria, up to 24months.

Locations

Country	Name	City	State
China	Eastern hepatobilliary surgery hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shen Feng

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR) per RECIST 1.1	Defined as patients achieving a complete response [CR] or partial response [PR]	Up to two years
Secondary	Progression free survival (PFS) per RECIST 1.1	Defined as the time from the start of treatment to the date of progressive disease, or death, whichever occurred first.	Up to two years
Secondary	Desease control rate (DCR) per RECIST 1.1	CR + PR + SD	Up to two years
Secondary	Overall survival (OS)	Defined as the time from the start of treatment to the date of death from any cause	Up to two years
Secondary	6mo PFS rate per RECIST 1.1	Progression-free survival (PFS) rate at 6 months	at 6 months
Secondary	adverse events	Include Treatment emerge adverse events, treatment related adverse events and serious adverse events	Up to two years