Trial Title:
Chiauranib in Patients With Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma
NCT ID:
NCT06492915
Condition:
Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Paclitaxel
Gemcitabine
Chiauranib
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:
Chiauranib
Description:
Chiauranib, 25 mg, 35 mg or 50 mg, oral administration once daily
Arm group label:
Chiauranib plus albumin-paclitaxel and gemcitabine
Intervention type:
Drug
Intervention name:
Albumin-paclitaxel Injection
Description:
Albumin-paclitaxel Injection, 125 mg/m^2 administered intravenously on Days 1, 8 and 15
of each 28-day cycle
Arm group label:
Chiauranib plus albumin-paclitaxel and gemcitabine
Intervention type:
Drug
Intervention name:
Gemcitabine Injection
Description:
Gemcitabine Injection, 1000 mg/m^2 administered intravenously on Days 1, 8 and 15 of each
28-day cycle
Arm group label:
Chiauranib plus albumin-paclitaxel and gemcitabine
Summary:
Chiauranib , which simultaneously targets against VEGFR/Aurora B/CSF-1R, several key
kinases involved in tumor angiogenesis, tumor cell mitosis, and chronic inflammatory
microenvironment.
Detailed description:
Chiauranib is a novel orally active multi-target inhibitor that simultaneously inhibits
the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRa and c-Kit),
mitosis-related kinase Aurora B and chronic inflammationrelated kinase CSF-1R in a high
potency manner with the IC50 at a single-digit nanomolar range. In particular, Chiauranib
showed very high selectivity in the kinase inhibition profile with little activity on
off-target non-receptor kinases, proteins, GPCR and ion channels, indicative of a better
drug safety profile in terms of clinical relevance.
This study is a phase II, single arm, open label, multi-center study to evaluate the
efficacy and safety of chiauranib plus albumin-paclitaxel and gemcitabine as first-line
therapy in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Understand and voluntarily sign the written informed consent form.
2. Age 18-75 years on the day of signing the informed consent form, male or female.
3. Histologically or cytologically confirmed unresectable locally advanced or
metastatic pancreatic ductal adenocarcinoma.
4. No prior systemic therapy for unresectable locally advanced or metastatic pancreatic
ductal adenocarcinoma. Subjects who have received prior induction chemotherapy,
concurrent radiotherapy, or adjuvant/neoadjuvant chemotherapy with curative intent,
the interval of recurrence or metastasis must be at least 6 months after the last
treatment.
5. At least one measurable lesion according to RECIST v1.1. Previously irradiated
lesions should not be selected as target lesions unless the previously irradiated
lesion as the only measurable lesion and is unequivocally progressive based on
imaging.
6. ECOG score 0 or 1.
7. Life expectancy≥3 months.
8. Major organ functions meet the following criteria: Hematology: hemoglobin≥90g/L,
absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets≥100×10^9/L(no haematopoietic
growth factors or blood transfusions and other medications considered by the
investigator to be corrective therapy, within 2 weeks before enrollment).
Biochemistry: serum creatinine≤1.5×ULN, total bilirubin≤1.5×ULN, AST/ALT≤2.5×ULN
(≤5×ULN for patients with hepatic metastasis). Coagulation Function: INR < 1.5×ULN.
Exclusion Criteria:
1. Histological or cytological confirmed other pathological types, such as acinar cell
carcinoma, neuroendocrine carcinoma, pancreablastoma, etc.
2. Previous received Aurora kinase inhibitors or systemic treatment of VEGF/VEGFR
inhibitors such as bevacizumab, sorafenib, sunitinib, amlotinib, apatinib, and
endostar.
3. Previous radiation therapy, chemotherapy, immunotherapy, targeted therapy within 28
days prior to the first dose. Traditional Chinese medicine (except for Chinese
herbal medicine) witn anti-malignancy effect judged by the investigator within 14
days prior to the first dose.
4. Presence of active or untreated brain metastases, meningeal metastases, spinal cord
compression, or molluscum contagiosum disease during the screening period. However,
enrolment is permitted for subjects who meet the following requirements and have
measurable lesion outside the CNS: asymptomatic after treatment and stable on
imaging for at least 4 weeks prior to the first dose (e.g., no new or enlarging
brain metastases) and have been off systemic glucocorticosteroids and anticonvulsant
medications for at least 2 weeks prior to the first dose.
5. Presence of clinically symptomatic pleural effusion, pericardial effusion or ascites
requiring frequent drainage (≥1 time/month) during the screening period.
6. Major surgery (craniotomy, thoracotomy, or laparotomy) or serious unhealed wounds,
ulcers, or fractures within 4 weeks prior to the first dose. Needle biopsy or other
minor surgery (except for intravenous infusion) within 7 days prior to the first
dose.
7. Significant arterial/venous thrombotic events within 6 months prior to first dose,
such as deep vein thrombosis and pulmonary embolism. Superficial vein thrombosis
without safety risk judged by the investigator is permitted.
8. Cardiac dysfunction or clinically meaningful cardiovascular disease, including:
(1)New York Heart Association (NYHA) grade II or higher congestive cardiac failure,
unstable angina pectoris, and/or myocardial infarction within the 6 months prior to
the first dose of the investigational drug, clinically significant arrhythmia unable
to be controlled with medical treatment or left ventricular ejection fraction (LVEF)
< 50% at screening. (2)Primary cardiomyopathies (e.g., dilated cardiomyopathy,
hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy,
restrictive cardiomyopathy, indeterminate cardiomyopathy). (3)Clinically significant
history of prolonged QTc interval, or QTcF interval >470ms for females or >450 ms
for males during the screening period. (4)Coronary heart disease with symptoms
requiring medication. (5)Documentation of hypertension treatment with≥3
antihypertensive medications simultaneously within 14 days before the first dose of
medication or systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90
mmHg during the screening period (resting state, measured approximately every 5
minutes, averaged after three consecutive measurements, rounded to the nearest
integer). (6)History of hypertensive crisis or hypertensive encephalopathy. (7)Other
cardiovascular disease judged by the investigator to be unsuitable for enrolment.
9. Active bleeding within 2 months prior to the first dose, or taking anticoagulants,
such as warfarin, phenprocoumon (prophylactic low-dose aspirin and low-molecular
heparin are permitted) during the screening period, or at high risk of bleeding
judged by the investigator during screening period (e.g., esophageal varix
associated with bleeding risk, locally active ulcer lesions, positive fecal occult
blood that can not exclude gastrointestinal bleeding, intermittent haemoptysis) .
10. Presence of significant gastrointestinal abnormalities during the screening period
that may interfere with drug intake, transit or absorption (e.g. inability to
swallow, chronic diarrhoea, post-small bowel resection or total gastrectomy),
according to the investigator's judgment.
11. History of gastrointestinal perforation and/or fistula, peptic ulcer disease,
intestinal obstruction (including incomplete intestinal obstruction that requires
parenteral nutrition), or biliary obstruction within 6 months prior to the first
dose.
12. History of other malignant tumors within 3 years prior to the first dose, except for
those treated with expected curative outcomes, such as basal cell carcinoma,
squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ
of the cervix, ductal carcinoma in situ of the breast, localized prostate cancer,
and papillary thyroid microcarcinoma.
13. For urine protein≥2+ by urinalysis during the screening period, a 24-hour urine
protein quantification test should be performed. The subject cannot be enrolled if
the quantified urine protein is≥1g/24 h. If the quantified urine protein is <1 g/24
h, the subject can still be enrolled.
14. Presence of peripheral neuropathy of CTCAE v5.0 criteria, Grade 2 or higher.
15. Known contraindications to albumin-paclitaxel and gemcitabine chemotherapy (see
descriptions for albumin-paclitaxel and gemcitabine).
16. Adverse effects of prior antineoplastic therapy that have not returned to ≤grade 1
of CTCAE v5.0 criteria (except for alopecia without safety risk judged by the
investigator and laboratory tests specified in Inclusion Criterion 8).
17. Presence of clinically active haemoptysis, active diverticulitis during the
screening period.
18. Presence of active tuberculosis during the screening period. Suspected subjects
should be excluded by a combination of chest imaging, sputum, and through clinical
signs and symptoms.
19. Presence of active hepatitis of positive HBsAg with positive viral replication or
positive HBcAb with positive viral replication during the screening period. Positive
HCV-Ab with positive viral replication. Positive of HIV. Active syphilis infection
(syphilis-specific antibody and nonspecific antibody positive). (Note: Priority for
qualitative detection and quantitative detection of viral replication when needed).
20. Previous or screening chest imaging showing the presence of interstitial lung
disease or pulmonary fibrosis or non-infectious pneumonitis requiring treatment, and
immune-associated pneumonia after previous treatment with PD-1/PD-L1 inhibitor.
21. Active infection during the screening period, including systemic anti-infective
therapy requiring oral or intravenous infusion within 2 weeks prior to the first
dose, unexplained fever (≥38°C, except for tumor causes judged by the investigator)
during the screening period.
22. Screening period or history of allogeneic organ transplantation and allogeneic
haematopoietic stem cell transplantation.
23. Unexplained weight loss of 5% or more between signing the ICF and the first dose.
24. NRS pain score 4 after analgesic medication during the screening period.
25. Severe central nervous system or psychiatric illness during the screening period.
26. Pregnant or lactating females. Female subjects of childbearing potential or male
subjects whose partners of childbearing potential are unable or unwilling to use
effective contraception (e.g., IUDs, Subcutaneous implant, sterilisation,
long-acting contraceptive injections, compound of short-acting oral contraceptives,
etc.) from 7 days prior to the first dose until 6 months after the end of treatment.
Female subjects of childbearing potential must have a blood pregnancy test negative
witnin 7days prior to the first dose.
27. During the screening period, the investigator deems other conditions unsuitable for
participation in this trial, such as clinically unacceptable worsening symptoms or
signs of pancreatic cancer progression, comorbidities, concurrent treatments, or any
laboratory abnormalities that may interfere with the assessment of efficacy and
safety outcomes.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
August 1, 2024
Completion date:
July 1, 2026
Lead sponsor:
Agency:
Chipscreen Biosciences, Ltd.
Agency class:
Industry
Source:
Chipscreen Biosciences, Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06492915
