Trial Title:
Surufatinib Plus Cadonilimab in Patients With Unresectable or Metastatic Bile Duct Adenocarcinoma
NCT ID:
NCT06092645
Condition:
Bile Duct Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Carcinoma, Ductal
Cholangiocarcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
surufatinib plus cadonilimab
Description:
Surufatinib: 250mg , po,qd, d1-d21, every 3 weeks for a treatment cycle. Cadonilimab:
10mg/kg, iv, d1, every 3 weeks for a treatment cycle
Arm group label:
surufatinib plus Cadonilimab
Other name:
surufatinib plus AK104
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntarily agree to participate in the study and sign the informed consent;
2. Over 18 years old (including 18 years old), regardless of gender;
3. Expected survival ≥12 weeks;
4. Within 7 days before the first administration of the study drug, the ECOG physical
status score was 0 or 1;
5. 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;
6. 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.
7. Patients who have Progression after first-line chemotherapy combined with PD-1/L1
inhibitors for advanced unresectable or metastatic bile duct adenocarcinoma
8. 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%;
9. 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;
10. 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.
11. Within 28 days prior to enrollment, women of reproductive age must confirm a
negative serum pregnancy test and consent to effective contraceptive use during the
study drug use period and within 60 days after the last dose. In this protocol,
women of reproductive age are defined as sexually mature women: 1) who have not
undergone hysterectomy or bilateral oophorectomy, 2) who have not had natural
menstrual cessation for 24 consecutive months (amenorrhea after cancer treatment
does not exclude fertility) (i.e., who have menstruated at any time during the
previous 24 consecutive months); Female spouses of male subjects of childbearing age
should also follow the above contraceptive requirements.
Exclusion Criteria:
Patients who meet any of the following conditions will not be admitted to the study:
1. 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.
2. Patients who are preparing for or have previously received an organ or allogeneic
bone marrow transplant;
3. 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;
4. 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).
5. 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);
6. 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;
7. 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;
8. Have clinical symptoms or diseases of the heart that are not well controlled, such
as:
1) 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); 9. Have high blood pressure that is not well
controlled by antihypertensive medication (systolic blood pressure ≥140mmHg or
diastolic blood pressure ≥90 mmHg (based on the average of BP readings taken from ≥2
measurements), allowing the above parameters to be achieved with antihypertensive
therapy; Hypertensive crisis or hypertensive encephalopathy in the past; 10. Major
vascular disease (e.g., aortic aneurysms requiring surgical repair or recent
peripheral arterial thrombosis) developed within 6 months prior to the start of
study therapy; 11. Severe, unhealed or open wounds and active ulcers or untreated
fractures; 12. Received major surgery within 4 weeks prior to the start of study
treatment (except for diagnosis) or expected to require major surgery during the
study period; 13. Inability to swallow tablets, malabsorption syndrome or any
condition affecting gastrointestinal absorption； 14. Evidence of abdominal gas that
cannot be explained by puncture or recent surgical procedures; 15. Past or current
central nervous system metastasis; 16. Be suffering from uncontrolled systemic
diseases, including diabetes mellitus, hypertension, pulmonary fibrosis, acute lung
disease, interstitial lung disease, cirrhosis of the liver, angina pectoris, severe
arrhythmia, etc.; 17. People with current or prior history of interstitial pneumonia
or interstitial lung disease requiring hormone therapy, or other pulmonary fibrosis,
institutional pneumonia (e.g., Subjects with bronchiolitis oblans), pneumoconiosis,
drug-related pneumonia, idiopathic pneumonia, or with evidence of active pneumonia
or severely impaired lung function on chest computed tomography (CT) images during
screening were allowed to have radiation pneumonia in the radiation field; Active
tuberculosis; 18. Presence of active autoimmune disease or history of autoimmune
disease with possible recurrence (including but not limited to: autoimmune
hepatitis, interstitial pneumonia, uveitis, enteritis, pituitaritis, vasculitis,
nephritis, hyperthyroidism, hypothyroidism [subjects controllable by hormone
replacement therapy only may be included]); Participants with non-systemic skin
diseases such as vitiligo, psoriasis, and alopecia, controlled type 1 diabetes
treated with insulin, or asthma in complete remission in childhood, were enrolled
without any intervention as adults; Patients with asthma requiring medical
intervention with bronchodilators were excluded; 19. Use of immunosuppressants or
systemic hormone therapy for immunosuppressive purposes within 14 days prior to
initiation of study therapy (dose>10mg/day prednisone or other equivalent hormone);
20. Use of strong CYP3A4/ CYP2C19 inducers including rifampicin (and its analogues)
and hypericum perforatum or strong CYP3A4/ CYP2C19 inhibitors within 14 days prior
to initiation of study therapy; 21. Known to have a history of severe allergy to any
monoclonal antibody or anti-angiogenesis targeting drug; 22. Severe infections,
including but not limited to hospitalization for complications of infection,
bacteremia, or severe pneumonia, in the 4 weeks prior to initiation of study
treatment; Oral or intravenous administration of therapeutic antibiotics within 2
weeks prior to starting study treatment (patients receiving prophylactic antibiotics
(for example, to prevent urinary tract infections or exacerbations of COPD) are
eligible for study participation； 23. Patients with congenital or acquired immune
deficiency (such as HIV infection); 24. Prior treatment with other
immunosuppressants (other than PD-1/L1 inhibitors) or prior treatment with tyrosine
kinase inhibitors; 25. To permit palliative radiotherapy for non-target lesions to
control symptoms, it must be completed at least 2 weeks prior to the initiation of
study therapy, and radiation-related adverse events have not recovered to ≤CTCAE
grade 1; 26. Has received live attenuated vaccines within 28 days prior to
initiation of study treatment, or is expected to require such vaccines during
treatment with cardonilizumab or within 60 days after the last administration of
cardonilizumab; 27. Received anti-tumor cytotoxic drug therapy, biologic drug
therapy (such as monoclonal antibodies), immunotherapy (such as interleukin-2 or
interferon), or other investigational drug therapy within 4 weeks prior to study
enrollment; 28. According to the investigator's judgment, the patient has other
factors that may affect the study results or lead to the forced termination of the
study, such as alcoholism, drug abuse, other serious diseases (including mental
illness) requiring combined treatment, serious laboratory abnormalities, and family
or social factors, which will affect the safety of the patient.
29. The toxicity of previous antitumor therapy has not returned to CTCAE level 0-1,
except in the following cases:
1. hair loss;
2. Pigmentation;
3. Peripheral nerve toxicity has returned to
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Recruiting
Contact:
Last name:
Jieer Ying, Doctor
Phone:
13858195803
Email:
hzyingjieer@163.com
Start date:
October 30, 2023
Completion date:
October 31, 2025
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06092645
