An Open-label, Single-arm, Multicenter, Phase II Clinical Study of Surufatinib Plus Cadonilimab as Second-line Therapy in Patients With Unresectable or Metastatic Bile Duct Adenocarcinoma

Zhejiang Cancer Hospital1 site in 1 country48 target enrollmentOctober 30, 2023

ConditionsBile Duct Adenocarcinoma

Interventionssurufatinib plus cadonilimab

Overview

Phase: Phase 2
Intervention: surufatinib plus cadonilimab
Conditions: Bile Duct Adenocarcinoma
Sponsor: Zhejiang Cancer Hospital
Enrollment: 48
Locations: 1
Primary Endpoint: Progression-free survival (PFS)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, single-arm, multicenter Phase II clinical study to evaluate the efficacy and safety of surufatinib combined with cardanilimab in second-line treatment of patients with inoperable or metastatic bile duct adenocarcinoma

Detailed Description

This is an open-label, single-arm, multicenter Phase II clinical trial. It is planned to enroll patients with inoperable or metastatic bile duct adenocarcinoma who have progressed through first-line chemotherapy combined with immunotherapy in several hospitals across the country to evaluate the efficacy and safety of second-line treatment with surufatinib Combination With Cadonilimab.

Registry

clinicaltrials.gov

Start Date

October 30, 2023

End Date

October 31, 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Zhejiang Cancer Hospital

Responsible Party

Principal Investigator

Ying Jieer

Zhejiang Cancer Hospital

Eligibility Criteria

Inclusion Criteria

•Voluntarily agree to participate in the study and sign the informed consent;
•Over 18 years old (including 18 years old), regardless of gender;
•Expected survival ≥12 weeks;
•Within 7 days before the first administration of the study drug, the ECOG physical status score was 0 or 1;
•Locally advanced or metastatic cholangiocarcinoma (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma) that is histologically and/or cytologically confirmed and is incurable and unresectable;
•The investigator confirmed the presence of at least one measurable lesion according to RECIST 1.1 criteria. Target lesions located within the field of prior radiotherapy or within the area following local treatment are considered measurable if they demonstrate progression.
•Patients who have Progression after first-line chemotherapy combined with PD-1/L1 inhibitors for advanced unresectable or metastatic bile duct adenocarcinoma
•Adequate organ function 1) Blood routine examination: (no transfusion within 14 days prior to screening, no use of granulocyte colony stimulating factor \[G-CSF\], no use of drug correction) : i. Neutrophils ≥1.5×109/L; ii. Platelet ≥75×109/L; iii. Hemoglobin ≥90g/L; 2) Biochemical examination: (no albumin infusion within 14 days prior to screening) : iv. Serum creatinine ≤1.5× upper limit of normal (ULN), or creatinine clearance \> 50 mL/min; v. Serum total bilirubin ≤1.5×ULN (subjects with Gilbert syndrome allow total bilirubin ≤3×ULN); vi. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤2.5×ULN; In subjects with liver metastasis, ALT and AST≤5×ULN; 3) Coagulation function: vii. International Standardized Ratio (INR) ≤2.3 or prothrombin time; (PT) exceeding the normal control range ≤6 seconds; 4) Urinary protein viii. Urinary protein \< 2+ (If urine protein ≥2+, it can be performed for 24 hours (h) Urinary protein quantification, 24h urinary protein quantification \< 1.0g can be included) 5) Heart function: ix. New York College of Cardiology (NYHA) rating \< 3; x. Left ventricular ejection fraction ≥50%;
•If the patient has active hepatitis B virus (HBV) infection: HBV-deoxyribonucleic acid (DNA) must be \< 500 IU/mL (\< 2500 copy/ml if the study center only has copy/ml testing units) and is willing to receive antiviral therapy throughout the study period; Hepatitis C virus (HCV) ribonucleic acid (RNA) positive patients must receive antiviral therapy according to standard local treatment guidelines and have liver function within CTCAE level 1 elevation;
•The patient must have an appropriate nutritional status, i.e. body mass index(BMI) ≥ 18 kg/m2, body weight ≥ 40 kg, and serum albumin ≥ 3.0 g/dL.

Exclusion Criteria

•Patients who meet any of the following conditions will not be admitted to the study:
•Active malignancy other than bile duct malignancy within 5 years or at the same time. Localized tumors that have been cured, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc.
•Patients who are preparing for or have previously received an organ or allogeneic bone marrow transplant;
•Moderate or severe ascites with clinical symptoms require therapeutic puncture or drainage (except those who only show a small amount of ascites without clinical symptoms on imaging); Uncontrolled or moderate or above pleural effusion and pericardial effusion;
•Study a history of gastrointestinal bleeding or a definite tendency to gastrointestinal bleeding within 6 months before the start of treatment, such as: Patients with bleeding risk or severe esophageal and gastric varices, locally active digestive ulcer lesions, and persistent positive occult blood in stool could not be included in the group (if the stool was positive for occult blood at baseline, it could be re-examined; if the stool was still positive after re-examination, gastroduodenal microscopy (EGD) was required; if EGD suggested bleeding risk, esophageal and gastric varices could not be included in the group).
•Known hereditary or acquired bleeding (e.g. coagulation disorders) or thrombotic tendencies, e.g. in hemophiliacs; Is currently or recently (within 10 days prior to the start of study therapy) used full dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic use of low-dose aspirin, low-molecular weight heparin permitted);
•Currently using or recently used (within 10 days before the start of study treatment) aspirin\>325 mg/ day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel, and cilostazole;
•Thrombosis or embolism events, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc., occurred within 6 months before the start of the study treatment;
•Have clinical symptoms or diseases of the heart that are not well controlled, such as:
•According to the New York Heart Association (NYHA) standards for Grade II or higher cardiac insufficiency or cardiac color ultrasound: LVEF (left ventricular ejection fraction) \<50%; 2) Unstable angina pectoris；3) Myocardial infarction occurred within 1 year before the start of study treatment；4) Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention；5) QTc\>450ms (male); QTc\>470ms (female) (QTc interval calculated by Fridericia formula; If the QTc is abnormal, it can be detected three times at an interval of 2 minutes, and the average value is taken);

Arms & Interventions

surufatinib plus Cadonilimab

Surufatinib: 250mg , po,qd, d1-d21, every 3 weeks for a treatment cycle. Cardonilimab: 10mg/kg, iv, d1, every 3 weeks for a treatment cycle

Intervention: surufatinib plus cadonilimab

Outcomes

Primary Outcomes

Progression-free survival (PFS)

Time Frame: up to 12 months

Refers to the date from the date of admission to the date of the first progression of disease or death of any cause, using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

Secondary Outcomes

Overall survival (OS)(up to 36 months)
Incidence of adverse events(Until the last medication for 30 days (±7 days) or before the start of other anti-tumor therapy (whichever occurs first))
Objective response rate(ORR)(up to 12 months)
Disease control rate (DCR)(up to 12 months)