Trial Title:
Pemigatinib Combined With Durvalumab for Previously Treated Biliary Tract Carcinoma
NCT ID:
NCT06530823
Condition:
Biliary Tract Carcinoma
Cholangiocarcinoma
Conditions: Official terms:
Carcinoma
Cholangiocarcinoma
Durvalumab
Conditions: Keywords:
biliary tract carcinoma
cholangiocarcinoma
FGFR mutation
targeted thearpy
immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pemigatinib and Durvalumab
Description:
Pemigatinib combined with Durvalumab Pemigatinib: 13.5mg, oral administration, once
daily, swallow the entire tablet with or without food. Take for 2 weeks and then
discontinue for 1 week. Durvalumab: 1500mg, intravenous infusion, once every three weeks.
Each infusion should take over 60 minutes.
Arm group label:
Pemigatinib and Durvalumab
Summary:
This study is a single-arm, multicenter Phase II clinical trial designed to preliminarily
assess the safety and efficacy of the combination therapy of pemigatinib and durvalumab
in the second-line treatment of patients with advanced malignant biliary tract cancer.
The study anticipates enrolling 38 participants characterized by the following criteria:
1) A confirmed diagnosis of advanced, metastatic, or unresectable biliary tract cancer by
histopathological examination; 2) Presence of FGFR2 fusion or rearrangement confirmed by
testing; 3) Prior receipt of first-line treatment for biliary tract cancer.
The primary questions the study aims to address are:
1. Can the combination of pemigatinib and durvalumab improve the prognosis of
participants with previously treated biliary tract cancer (BTC)?
2. What is the safety profile of the treatment with pemigatinib and durvalumab?
Participants will receive:
1. Oral administration of 13.5 mg pemigatinib once daily, in combination with
durvalumab 1500 mg via intravenous infusion.
2. Follow-up visits will be scheduled every 6 weeks.
Investigators will observe and document the objective tumor response rate of the
participants, as well as progression-free survival (PFS), disease control rate (DCR),
overall survival (OS), and adverse events.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥18 years, men and women;
2. ECOG performance status of 0-1;
3. Histologically confirmed advanced gallbladder cancer or cholangiocarcinoma patients
who have received one prior line of therapy;
4. Adult patients with advanced, metastatic, or unresectable cholangiocarcinoma or
gallbladder cancer confirmed to have FGFR2 fusion or rearrangement;
5. Diagnosed with locally advanced disease according to the 8th edition of AJCC, with
clinical staging of cT3/4NxM0/1 for gallbladder cancer, intrahepatic
cholangiocarcinoma, or hilar cholangiocarcinoma, or cT2N2M0, cT3/4NxM0/1 for distal
cholangiocarcinoma based on enhanced CT or MRI;
6. Use of contraception during the study period;
7. Life expectancy ≥3 months;
8. All patients must provide tumor tissue specimens (fresh or paraffin-embedded) for
FGFR2 expression analysis before enrollment and after surgery (5 slides within 3
years are required);
9. At least one measurable lesion according to RECIST 1.1 criteria, which has not been
irradiated;
10. Within 7 days prior to the first administration of the study drug, the organ
function levels of the enrolled patients must meet the following requirements:
1. Hematopoietic function: Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet
count (PLT) ≥ 100×10^9/L, hemoglobin (Hb) ≥90g/L, and no blood transfusion or
component blood transfusion within 14 days prior to testing;
2. Hepatic function: Serum total bilirubin (TBIL) ≤1.5 times the upper limit of
normal (ULN), aspartate aminotransferase (AST), alanine aminotransferase (ALT),
and alkaline phosphatase (APK) ≤2.5 times ULN, serum creatinine ≤1.5 times ULN
and creatinine clearance (based on the Cockcroft-Gault formula) ≥50mL/min,
serum albumin (ALB) ≥30g/L, Child-Pugh class A;
3. Coagulation function: For patients not receiving anticoagulant therapy,
international normalized ratio (INR), activated partial thromboplastin time
(APTT) ≤1.5 times ULN; patients receiving anticoagulant therapy should maintain
therapeutic levels of anticoagulants;
4. Thyroid function: Thyroid-stimulating hormone (TSH) ≤1×ULN, if TSH
>1×ULN, free T3 (FT3) and free T4 (FT4) levels should also be assessed,
and if normal, the patient may be enrolled;
5. Renal function: Urine protein ≤1+. If urine protein >1+, a 24-hour urine
protein test is required, and the total amount must be ≤1 gram for enrollment;
6. Normal cardiac function, i.e., normal electrocardiogram or clinically
insignificant abnormalities, and left ventricular ejection fraction (LVEF)
>50% as shown by echocardiography;
11. Serum pregnancy test results must be negative within 7 days prior to the first
administration of the trial medication for women of childbearing age; men with
reproductive capacity or women who may become pregnant must use highly effective
contraception (e.g., oral contraceptives, intrauterine devices, abstinence, or
barrier methods combined with spermicides) throughout the trial and continue for 12
months after treatment;
12. Volunteers willing to participate in the study, sign the informed consent form, have
good compliance, and cooperate with follow-up.
Exclusion Criteria:
1. Patients who have not received standard first-line treatment for advanced biliary
tract tumors;
2. Pregnant or breastfeeding women, and women of childbearing age with positive
pregnancy test results at baseline;
3. Patients diagnosed with central nervous system metastasis by CT/MR/PET-CT;
4. Patients who have previously received live vaccine administration or other antitumor
treatments such as radiotherapy;
5. Patients who have participated in or are currently participating in other drug or
therapy clinical trials within 4 weeks prior to the first administration of the
study medication;
6. Patients who have undergone major surgical procedures within 4 weeks prior to the
first administration of the study medication or have not recovered from the side
effects of such surgery, or patients who have undergone radiotherapy within 2 weeks
prior to the first administration of the study medication;
7. Patients with any primary immunodeficiency, active autoimmune disease, or history of
autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial
pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis,
hyperthyroidism, vitiligo, patients with a history of asthma who have completely
resolved in childhood and do not require any intervention in adulthood may be
included; patients with asthma requiring medical intervention with bronchodilators
are excluded;
8. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation, and patients currently using immunosuppressants or
corticosteroids for immunosuppressive purposes (dosage >10mg/day prednisone
or other equivalent corticosteroids) and still in use within 2 weeks prior to
enrollment;
9. Patients with other malignancies within the past 5 years, except for cured skin
basal cell or squamous cell carcinoma, superficial bladder cancer, early prostate
cancer, in situ cervical cancer, or breast cancer;
10. Patients who have received hematopoietic growth factors within 1 week prior to the
first administration of the study medication, such as granulocyte colony-stimulating
factor (G-CSF), erythropoietin, etc.;
11. Patients with positive HIV antibodies or syphilis antibodies, and patients with
active hepatitis B or C;
12. Known allergies to recombinant humanized PD-L1 monoclonal antibody drugs and their
components;
13. Patients with symptomatic pleural effusion, pericardial effusion, or ascites
requiring clinical treatment;
14. Patients with severe cardiovascular diseases within the last 12 months, such as
clinically significant coronary heart disease, NYHA≥II congestive heart failure,
uncontrolled arrhythmias, myocardial infarction;
15. Within 6 months prior to the first administration of the study medication, the
following conditions have occurred: deep vein thrombosis or pulmonary embolism;
myocardial infarction; severe or unstable arrhythmias or angina; percutaneous
coronary intervention, acute coronary syndrome, coronary artery bypass grafting;
cerebrovascular accident, transient ischemic attack, cerebral embolism.
16. Patients who have undergone any type of gastrointestinal surgery, or have upper
gastrointestinal obstruction, bleeding, digestive dysfunction, or malabsorption
syndrome that may affect the absorption of the study medication;
17. Concurrent severe uncontrollable infections or other severe uncontrollable
comorbidities, moderate or severe renal impairment;
18. Active pulmonary diseases, such as interstitial pneumonia, pneumonia, chronic
obstructive pulmonary disease, asthma, or a history of active tuberculosis.
19. Abnormal coagulation function (INR>2.0, PT>16s), with a tendency to
bleed or currently receiving thrombolytic or anticoagulant therapy, prophylactic use
of low-dose aspirin, low molecular weight heparin is allowed;
20. Significant clinical bleeding symptoms or a clear tendency to bleed within 3 months,
such as coughing or expectorating blood ≥2.5ml, history of gastrointestinal
bleeding, esophageal and gastric varices with bleeding risk, bleeding gastric ulcers
or patients with vasculitis, etc.; if the baseline fecal occult blood test is
positive, it can be retested, and if it is still positive after retesting, a
gastroscopy is required, and if gastroscopy indicates severe esophageal and gastric
varices, the patient may not be enrolled (patients who have undergone gastroscopy
within 3 months and excluded such conditions are excluded);
21. Known genetic or acquired bleeding and thrombotic tendencies, such as hemophilia,
coagulation disorders, thrombocytopenia, etc.;
22. History of substance abuse that cannot be quit or history of mental disorders.
23. Use of warfarin or any other coumarin derivative anticoagulants within 14 days prior
to the first administration of the study medication.
24. Other severe, acute, or chronic medical diseases or laboratory abnormalities that
the investigator judges may increase the risk associated with participating in the
study or may interfere with the interpretation of the study results.
25. Patients deemed to have poor compliance by the investigator, or other conditions
that make them unsuitable for participating in this trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
August 1, 2024
Completion date:
August 1, 2028
Lead sponsor:
Agency:
Eastern Hepatobiliary Surgery Hospital
Agency class:
Other
Source:
Eastern Hepatobiliary Surgery Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06530823
