Trial Title:
Surufatinib Combined With Gemcitabine Plus Nab-paclitaxel in Locally Advanced Pancreatic Cancer
NCT ID:
NCT06361030
Condition:
Pancreatic Cancer
Pancreatic Cancer Non-resectable
Pancreatic Ductal Adenocarcinoma, PDAC
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Paclitaxel
Gemcitabine
Conditions: Keywords:
Pancreatic ductal adenocarcinoma
surufatinib
surgical conversion
gemcitabine
nab-paclitaxel
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:
surufatinib combined with gemcitabine plus nab-paclitaxel
Description:
Surufatinib capsules: oral, once daily. Combination treatment period: 200 mg each time,
every 4 weeks for a treatment cycle(Q4W). If all the chemotherapy drugs were stopped
during the maintenance treatment period, only surufatinib was left, the dose of
Surufatinib could be increased to 300 mg per dose according to the patient's
condition.
Gemcitabine: iv, 1000 mg/m2, days 1, 8, and 15 of each treatment cycle, Q4W. Paclitaxel
(albumin-bound), iv, 125mg/m2, on days 1, 8 and 15 of each treatment cycle, Q4W.
All they will be used until disease progression, death, intolerable toxicity, initiation
of new antineoplastic therapy, withdrawal of consent, loss to follow-up, or any other
protocol-specified event requiring treatment discontinuation or study closure, whichever
occurred first.
But If surgical resection was performed, they will be only maintained for 6 months after
surgery.
Arm group label:
Experimental Group
Summary:
To evaluate the efficacy and safety of surufatinib combined with gemcitabine plus
nab-paclitaxel in patients with locally advance d pancreatic cancer
Detailed description:
Pancreatic ductal adenocarcinoma (PDAC) has a very poor prognosis. Currently, there is no
standard treatment for locally unresectable PDAC, and clinical research and conversion
therapy are encouraged by guidelines. Whether it is conversion or palliative
chemotherapy, in fact, the choice of chemotherapy is based on the existing first-line
regimens of metastatic PDCA. Gemcitabine combined with nab-paclitaxel is one of the
preferred first-line chemotherapy regimens for metastatic or locally advanced PDAC.
However, the conversion rate of gemcitabine combined with nab-paclitaxel is not ideal
according to the current results. The aim of this study is to investigate whether the
combination of gemcitabine and nab-paclitaxel with surufatinib can improve the surgical
conversion rate.
This is a prospective, single-arm exploratory clinical study. A safety run-in period of 6
patients will be set. After 4-6 cycles of induction therapy with gemcitabine and
nab-paclitaxel plus surufatinib, if become operable, the therapy will be continued for
another 6 months after surgery; if not operable, the therapy will be also continued as
long as no PD during induction therapy. If PD occurs, it will enter second-line therapy.
Surufatinib capsule will be administered orally 200mg, once daily, a 4-week treatment
cycle(Q4W) during combined with gemcitabine and nab-paclitaxel. If all chemotherapy drugs
are stopped during the maintenance treatment period and only surufatinib is left, the
dose of surufatinib can be increased to 300 mg per dose according to the patient's
condition. Gemcitabine and nab-paclitaxel plus surufatinib will be used until disease
progression, death, intolerable toxicity, initiation of new antineoplastic therapy,
withdrawal of informed consent, loss of follow-up, and other conditions that require
treatment discontinuation or the study is completed. Whichever comes first. If surgical
resection was performed, it will be maintained for 6 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The subjects voluntarily joined the study and signed the informed consent, with good
compliance and follow-up;
2. Aged 18-75 years old (including 18 and 75 years old)
3. male or female
4. Histologically or cytologically confirmed adenocarcinoma of the pancreas
5. Unresectable pancreatic cancer according to radiographic criteria (CT or MRI scans)
or exploration( NCCN guidelines were referred): (1)The portal and superior
mesenteric vein could not be reconstructed safely due to tumor invasion, venous
occlusion, or involvement of a large area of the superior mesenteric vein jejunal
branch (2)If pancreatic head/uncinate tumor: tumor contacts superior mesenteric
artery or celiac trunk artery >180 degrees. If pancreatic body tail tumor: tumor
contacts the superior mesenteric artery or celiac trunk artery>180 degrees, and
tumor contacts the celiac trunk artery and infiltrates the abdominal aorta.
6. Without distant metastasis as defined by CT or MRI scan of the chest, abdomen and
pelvis
7. No prior systematic treatment for advanced pancreatic cancer
8. At least one measurable lesion was required. (Response evaluation criteria in Solid
Tumors, RECIST, version 1.1)
9. ECOG performance status of 0 or 1
10. Expected survival ≥12 weeks
11. Acceptable organ and bone marrow function, laboratory values within 7 days prior to
enrollment (no blood components, cell growth factors, albumin, or other corrective
medications were allowed within 14 days prior to laboratory testing), as follows:
(1)Blood routine: neutrophils ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L, hemoglobin ≥
9.0g/dL; (2) Liver function: serum total bilirubin ≤ 1.5 x ULN; aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN in
subjects without liver metastases, AST and ALT levels ≤5 × ULN in subjects with
documented liver metastases; (3) Renal function: serum creatinine ≤ 1.5 x ULN, or
creatinine clearance (CCr) ≥ 50mL/min; Urine protein < 2 +; if urine protein
≥2+ at baseline, 24-hour urine collection should be done and 24-hour urine protein
< 1g; (4) Coagulation function: international normalized ratio (INR) and
activated partial thromboplastin time (APTT) ≤ 1.5 times ULN.
12. Female subjects of childbearing potential or male subjects whose sexual partner is a
female of childbearing age should take effective contraceptive measures during the
whole treatment period and 6 months after the last treatment.
Exclusion Criteria:
1. Participants had a second primary malignancy detected prior to the first dose of
study treatment, or has other malignancies diagnosed within 5 years prior to the
first dose of study treatment, with the exception of radically treated basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, and/or radically
resected carcinoma in situ;
2. Allergy to study medication or excipients
3. With dysphagia or known malabsorption of drugs
4. Have participated in any other drug clinical trial and received the corresponding
trial drug within the previous 4 weeks. Or are participating in other clinical
studies that may interfere with this study.
5. Drug-uncontrolled hypertension；systolic blood pressure ≥140 mmHg and/or diastolic
blood pressure ≥90 mmHg; History of hypertensive crisis or hypertensive
encephalopathy.
6. Patients with active gastric or duodenal ulcer, ulcerative colitis, intestinal
obstruction, other gastrointestinal diseases, or active bleeding from unresectable
tumors before enrollment, or other conditions that may cause gastrointestinal
bleeding or perforation as judged by the investigator; Or have a history of bowel
perforation or fistula and do not fully recover from surgery.
7. Patients had a history of arterial or deep-vein thrombosis within 6 months before
enrollment ，or had evidence or history of bleeding tendency, regardless of severity,
within 2 months before enrollment.
8. Stroke or transient ischemic attack occurred within 12 months before enrollment.
9. Incomplete healing of skin wounds, surgical sites, trauma sites, severe mucosal
ulcers, or fractures.
10. Active bacterial, viral, or fungal infections requiring systemic treatment, defined
as signs/symptoms associated with the infection that persist and do not improve
despite appropriate antibiotic, antiviral, and/or other treatments
11. Known hepatitis B or C infection or a history of human immunodeficiency virus (HIV)
infection ; Subjects receiving immunosuppressive or myelosuppressive drugs is
considered to be associated with an increased risk of severe neutropenia
complications by the investigators.
12. Severe cardiovascular disease, including unstable angina or myocardial infarction,
occurred within 6 months before enrollment; Clinically significant cardiovascular
disease, including but not limited to acute myocardial infarction, severe/unstable
angina, or coronary artery bypass grafting within 6 months before enrollment; New
York Heart Association (NYHA) classification of congestive heart failure >Grade 2;
Ventricular arrhythmias requiring medical therapy; LVEF(left ventricular ejection
fraction)<50%. Electrocardiogram (ECG) corrected QT interval ≥480 msec.
13. Clinically significant ascites
14. Clinically significant electrolyte disturbances.
15. Severe mental illness that may compromise the safety of the subjects or the
integrity of the study data.
16. Any clinical or laboratory abnormalities or adherence that were deemed by the
investigator to be inappropriate for participation in the trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430000
Country:
China
Contact:
Last name:
Heshui Wu
Phone:
+86 137-2011-7761
Email:
heshuiwu@hust.edu.cn
Investigator:
Last name:
Heshui Wu
Email:
Principal Investigator
Start date:
June 1, 2024
Completion date:
June 1, 2027
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06361030
