Trial Title:
Pemigatinib Combined With PD-1 Inhibitor in Unresectable or Metastatic Intrahepatic Cholangiocarcinoma
NCT ID:
NCT05913661
Condition:
Carcinoma
Intrahepatic Cholangiocarcinoma
Digestive System Neoplasms
PD-1 Inhibitor
First-line Treatment
Conditions: Official terms:
Cholangiocarcinoma
Digestive System Neoplasms
Gastrointestinal Neoplasms
Immune Checkpoint Inhibitors
Conditions: Keywords:
unresectable intrahepatic cholangiocarcinoma
metastatic intrahepatic cholangiocarcinoma
first-line treatment
Pemigatinib
PD-1 inhibitor
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:
Pemigatinib
Description:
Pemigatinib is scheduled to be administered at a dose of 13.5 mg quaque die according to
a 2-week dosing and 1-week discontinuation regimen.
Arm group label:
pemigatinib combined with PD-1 inhibitor
Other name:
Pemazyre
Intervention type:
Drug
Intervention name:
PD-1 Inhibitors
Description:
The dosing regimen is 200 mg IV Q3W
Arm group label:
pemigatinib combined with PD-1 inhibitor
Other name:
Sintilimab
Summary:
This is a Prospective, single-arm, phase II study with multicenter participation. The
objective of this study is to evaluate the efficacy and safety of pemigatinib combined
with PD-1 inhibitor as first-line treatment for patients with advanced unresectable or
metastatic intrahepatic cholangiocarcinoma.
Detailed description:
The study will be divided into two phases. The first phase is the safety import phase, in
which three subjects with intrahepatic cholangiocarcinoma will be enrolled to receive a
Scheduled dose of pemigatinib for one course of treatment， If the initial three subjects
didn't develop DLT during the 21-day observation period, the dose will be considered
tolerable and the study will proceed to Part II, otherwise, the dose will be adjusted and
the evaluation will continue according to the above criteria.
A total of 30 subjects will be enrolled in Phase II of the study, and all
screening-qualified subjects will receive pemigatinib combined with PD-1 inhibitor.
pemigatinib and PD-1 inhibitors will be administered at established doses according to a
regimen until progressive disease, intolerable toxicity, or informed consent form has
been withdrawn. PD-1 inhibitors will be administered for a maximum of 24 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Local advanced, recurrent, or metastatic cholangiocarcinoma confirmed by histology
or cytology and judged as unresectable by imaging and clinical diagnosis;
2. Have not received systematic treatment in the past;
3. The existence of FGFR2 fusion/rearrangement was confirmed by gene detection;
4. Male or female aged ≥ 18 years;
5. According to RECIST v1.1, there is at least one measurable target lesion. And the
target lesion has not received local treatment;
6. No other anti-tumor treatment was received within 4 weeks before the first use of
the study drug;
7. Life expectancy ≥ 12 weeks;
8. Eastern Oncology Collaboration group (ECOG) physical condition (PS) score 0-1;
9. Having sufficient organ and bone marrow function reserve, which is defined as
follows:(1)Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelet count (PLT) ≥ 80 ×
109/L Hemoglobin content (HGB) ≥ 9.0 g/dL. G-CSF, GM-CSF, red blood cell infusion,
and platelet infusion were not used within 14 days before the examination; (2)Liver
function requirement for patients without liver metastasis: serum total bilirubin
(TBIL) ≤ 1.5 × Upper limit of normal (ULN); Alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) ≤ 2.5 × ULN; Requirements for patients with liver
metastasis or intrahepatic cholangiocarcinoma: serum TBIL ≤ 1.5 × ULN; ALT and AST ≤
5 × ULN; (3)Renal function: creatinine clearance rate (Ccr) ≥ 50 mL/min (calculated
by Cockcroft/Default formula): female: CrCl=(0.85 × (140 - Age) × (Weight)/(72 ×
Serum creatinine (mg/dL), male: CrCl=(140 age) × (Weight)/(72 × Serum creatinine
(mg/dL); (4)Sufficient blood coagulation function, defined as the international
standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; If the subject is
receiving anticoagulation treatment, it is acceptable as long as PT is within the
scope of anticoagulation drugs;
10. Female subjects of reproductive age or male subjects with female sexual partners of
reproductive age shall take effective contraceptive measures during the whole
treatment period and 6 months after the treatment period.
Exclusion Criteria:
1. Previously received selective FGFR inhibitor treatment, excluding pan target
inhibitors such as Anlotinib and Lenvatinib
2. Received immunosuppressive drugs within 4 weeks before the first administration of
the trial treatment, excluding local glucocorticoids or systemic glucocorticoids of
physiological dose by nasal spray, inhalation, or other means (i.e. no more than 10
mg/day prednisone or other glucocorticoids of equivalent dose).
3. Received live attenuated vaccine within 4 weeks before the first administration of
the trial treatment or during the study period.
4. Received any other study drug treatment or participated in interventional clinical
research 4 weeks before the first administration of the trial treatment;
5. Before the first administration of the trial treatment, there was toxicity caused by
previous anti-tumor treatment that was not restored to the level 0 or 1 of the
National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI
CTCAE Version 5.0) (excluding alopecia, non-clinically significant laboratory
abnormalities, and asymptomatic laboratory abnormalities).
6. Active, known or suspected autoimmune disease, or history of autoimmune disease in
the past 2 years (patients with vitiligo that do not need systematic treatment,
psoriasis, alopecia, or Graves' disease in the past 2 years, hypothyroidism who only
need thyroid hormone replacement therapy and type I diabetes who only need insulin
replacement therapy can be enrolled).
7. Known history of primary immunodeficiency.
8. Known to have active pulmonary tuberculosis.
9. Known Symptomatic central nervous system metastases and/or carcinomatous meningitis.
For patients with brain metastasis who have received treatment in the past, if their
condition is stable (no evidence of imaging progress is found at least 4 weeks
before the first administration of the trial treatment), and repeated imaging
examination proves that there is no evidence of new brain metastasis or enlargement
of the original brain metastasis focus, and they do not need steroid treatment at
least 14 days before the first administration of the trial treatment, they can
participate in the trial. This exception does not include carcinomatous meningitis,
regardless of its clinical stability should be excluded.
10. Medical history of other primary malignant tumors, except: (1)malignant tumors that
have completely alleviated for at least 5 years before enrollment and do not require
other treatment during the study period; (2)Fully treated non-melanoma skin cancer
or malignant lentigo without evidence of disease recurrence; (3)Fully treated
carcinoma in situ without evidence of disease recurrence.
11. During pregnancy or lactation.
12. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation.
13. The following abnormal laboratory parameters: (1) Serum phosphate > ULN, and
considered clinically significant by the investigator; (2) Serum calcium > ULN, or
when serum albumin exceeds the normal range, the corrected calcium concentration of
serum albumin exceeds the normal upper limit.
14. Known history of human immunodeficiency virus (HIV) infection or confirmed positive
immune test result.
15. Known active serious infections or poorly clinically controlled infections.
16. Pleural fluid, ascites, or pericardial effusion with obvious clinical symptoms and
requiring drainage.
17. Patients with acute or chronic active hepatitis B or hepatitis C, whose hepatitis B
virus (HBV) DNA>2000 IU/ml or 10^4 copies/ml, or Hepatitis C virus (HCV) RNA>10^3
copies/ml, or Hepatitis B surface antigen (HBsAg) and anti HCV antibody were both
positive. If laboratory parameters can be reduced to lower than the above standards
after nucleotides antiviral treatment, the patient can be enrolled.
18. Clinically significant or uncontrolled heart diseases, including unstable angina,
acute myocardial infarction within 6 months before the first administration of the
trial treatment, New York Heart Association(NYHA) III/IV congestive heart failure,
and uncontrolled arrhythmia (subjects with a pacemaker or atrial fibrillation with
well-controlled heart rate can be enrolled).
19. There are ECG changes or medical history that the researchers consider clinically
significant; For screening subjects with QTcF interval>480 ms and indoor conduction
block (QRS interval>120 ms), JTc interval can be used to replace QTc interval after
being approved by the sponsor (if so, JTc must be ≤ 340 ms).
20. Uncontrolled hypertension, systolic pressure>160 mmHg or diastolic pressure>100 mmHg
after optimal medical treatment, hypertension crisis, or hypertensive encephalopathy
history.
21. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh B or more severe
cirrhosis.
22. Patients with interstitial lung disease.
23. Major surgery (craniotomy, thoracotomy, or laparotomy) was performed within 4 weeks
before the first administration of the trial treatment, or major surgery was
expected to be performed during the study treatment.
24. Before starting treatment, the toxicity and/or complications of major surgery have
not been fully recovered.
25. Pregnant or lactating females, or subjects who are expected to be pregnant or give
birth during the study period from the screening follow-up to the completion of the
safety follow-up (male subjects to 90 days after the last administration of the
trial treatment).
26. Received radiotherapy within 4 weeks before the first administration of the trial
treatment. The radiotherapy-related toxicity of the subject must have been fully
recovered, and no corticosteroid treatment is required. It is confirmed that
radiation pneumonia is excluded. For palliative radiotherapy for non-CNS diseases, a
2-week washout period is allowed.
27. History of disorder of calcium and phosphorus metabolism, or systemic electrolyte
metabolism imbalance with ectopic calcification of soft tissues (excluding
calcification of soft tissues such as skin, kidney, tendon, or blood vessel without
systemic electrolyte metabolism imbalance caused by injury, disease, advanced age,
and other reasons).
28. Corneal or retinal diseases with clinical significance confirmed by ophthalmological
examination.
29. Received any potent CYP3A4 inhibitor or inducer was used 14 days or within 5
half-lives (whichever is shorter) before the first administration of the trial
treatment. Ketoconazole is allowed for external use.
30. Known allergic reaction to pemigatinib or the excipients of the study drug
pemigatinib.
31. Known hypersensitivity to any monoclonal antibody.
32. The investigator considered that the subject could not comply with the
administration arrangement and study evaluation.
33. Unable to understand or unwilling to sign the Informed Consent Form (ICF).
34. Unable or unwilling to swallow pemigatinib or suffering from significant digestive
system diseases that may interfere with absorption, metabolism, or excretion.
35. Known history of vitamin D deficiency and needed to supplement vitamin D beyond the
physiological dosage (except for vitamin D dietary supplements).
36. Other acute or chronic diseases, mental diseases, or abnormal laboratory parameters
that may lead to the following results: increase the risk related to the study
participation or study drug administration, or interfere with the interpretation of
the study results, and the patient is listed as ineligible to participate in the
study according to the judgment of the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Lei Zhang
Address:
City:
Guangzhou
Zip:
510220
Country:
China
Status:
Recruiting
Contact:
Last name:
Lei Zhang, PHD
Phone:
+8613602730646
Email:
zhangl9@mail.sysu.edu.cn
Start date:
July 2023
Completion date:
November 2024
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
First Affiliated Hospital of Jinan University
Agency class:
Other
Collaborator:
Agency:
Shenzhen University General Hospital
Agency class:
Other
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05913661
