Clinical trial NCT05168527: The First Line Treatment of Fruquintinib Combined With Albumin Paclitaxel and Gemcitabine in Pancreatic Cancer Patients
Official title: An Open Single-center Phase II Clinical Study of Fruquintinib Combined With Chemotherapy in Patients With Liver Metastases From Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Pancreatic Cancer
Safety and Effectiveness
TKI
Chemotherapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2021-12-23
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the safety and effectiveness of Fruquintinib combined with Albumin Paclitaxel and Gemcitabine on pancreatic cancer patients with liver metastases. Plan to enrollment 30 patients.

Detailed description: Pancreatic cancer is the most deadly malignant tumor commonly found in the digestive system and is known as the king of cancer. According to the global cancer statistics released in 2018, there are about 458,900 new cases of pancreatic cancer worldwide each year, and the number of deaths due to pancreatic cancer each year is about 432,200. The data of pancreatic cancer collected by the National Cancer Center of China in 2019 showed that the incidence rate was 6.92 per 100,000, and new cases accounted for about 4.31% of all malignant tumors, ranking 10th; the case fatality rate was 6.16 per 100,000, with deaths every year It accounts for about 3.78% of all malignant tumors, ranking 7th. Compared with urban areas and rural areas, the morbidity and mortality have increased compared with previous years. The incidence of pancreatic cancer has been increasing year by year worldwide, and it is expected that by 2030, it will surpass colorectal cancer and breast cancer to become the second cancer-fatal tumor. Pancreatic cancer is extremely malignant, with a 5-year survival rate of only 9%, and its case fatality rate is basically equal to the incidence rate. The case fatality rate of pancreatic cancer may continue to rise, which will seriously threaten and affect human health.

The specific etiology and pathogenesis of pancreatic cancer are currently unclear, the early clinical manifestations are not obvious, the rapid development, the extremely high degree of malignancy, and the poor prognosis, all of which lead to the refractory and high mortality of pancreatic cancer. It is precisely because the early symptoms are not typical and the clinical signs are not obvious, most patients are already in the locally advanced stage or have distant metastases when they are diagnosed.In this case, the chance of surgical treatment is low and the effect is not ideal. 80% of pancreatic cancer patients are already in the inoperable advanced stage at the time of diagnosis, and more than 50% of them have found metastases at the time of diagnosis, and have lost the chance of radical surgery. The most common distant metastasis site is the liver. At present, for patients with liver metastases from pancreatic cancer, the standard treatment regimen in domestic and foreign guidelines is palliative treatment based on chemotherapy.

According to the latest updated treatment guidelines for metastatic pancreatic cancer by the American Society of Clinical Oncology (ASCO), the first-line chemotherapy regimen should be selected based on the patient's physical status. For patients with good physical status, a combination regimen may be considered, and patients with poor physical status should choose single-agent chemotherapy. Or the best supportive treatment. For those with good physical status, FOLFIRINOX, gemcitabine and paclitaxel are recommended; for patients with poor physical status, single-agent gemcitabine can be used. If tolerable, they can be combined with albumin paclitaxel or calciner under the guidance of an experienced oncologist. Petabine or erlotinib. Overall, the median OS of first-line chemotherapy did not exceed 12 months, and the median OS of second-line chemotherapy ranged from 3.3 to 9.9 months. Therefore, the overall treatment effect of pancreatic cancer was poor, and the median survival was only 6 months. For 8 months, the effect was not good. All major guidelines recommend the development of multi-center clinical studies to prolong patient survival and discover new effective drugs. In summary, actively exploring new comprehensive treatment strategies, breaking through treatment options for advanced pancreatic cancer, improving the survival time of patients with liver metastases of pancreatic cancer, and exploring the biological characteristics of liver metastases of pancreatic cancer are important clinical issues that urgently need to be resolved.

Eligibility criteria: Inclusion Criteria:

1. Age≥18 years old;
2. Pancreatic cancer was confirmed by pathology or cytology;
3. Liver-metastatic confirmed by pathology or clinical imaging;
4. Newly treated patients who have not received any systemic treatment for pancreatic cancer are allowed to enter the group for patients who have previously used fluorouracils (excluding gemcitabine and or taxanes) as adjuvant treatments for recurrence;
5. ECOG score of preoperative physical condition was 0-1;
6. Expected survival time ≥3months;
7. There is at least one measurable lesion under CT evaluation according to the RECIST 1.1 standard,;
8. The patient has sufficient hematological function (not receiving blood, platelet transfusion or growth factor supportive therapy within 14 days before the start of the study treatment), determined according to the following laboratory test values:

   1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;
   2. Platelets ≥ 100 × 109/L;
   3. Hemoglobin ≥ 9.0 g/dL;
9. The patient has sufficient liver and kidney function, which is determined according to the following laboratory test values:

   1. Serum creatinine ≤ 1.5 × ULN;
   2. If serum creatinine\>1.5 × ULN, creatinine clearance rate ≥50ml/min;
   3. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) in non-liver metastatic lesions ≤ 2.5 × ULN, and AST and ALT ≤ 5.0 × ULN in liver metastatic lesions;
   4. Serum albumin ≥ 2.5 g/dL;
   5. Total bilirubin ≤1.5 × ULN;
10. Men, women of childbearing age (postmenopausal women who must have been menopausal for at least 12 months to be considered infertile) and their partners voluntarily take it during treatment and at least six months after the last study drug is taken by the investigator. Effective contraceptive measures;
11. Able to understand and voluntarily sign a written informed consent form and voluntarily complete the research procedures and follow-up inspections. The informed consent form must be signed before the implementation of any research procedures specified by the trial

Exclusion Criteria:

1. Received chemotherapy within 14 days before entering the study.
2. Received VEGFR signaling pathway therapy or other anti-cancer therapy within 14 days before enrollment.
3. Received radiotherapy within 14 days before enrollment, and received chest radiotherapy within 28 days before enrollment.
4. Active central nervous system involvement is known.
5. Oral anticoagulant is being used, or an inhibitor or inducer of potent cytochrome oxidase 3A4 (CYP3A4) is being used (see Appendix 1 for details). Allow the use of subcutaneous anticoagulants.
6. Patients who have participated in clinical trials of reagents or new drugs under investigation within 28 days before the first treatment administration (phase I-IV clinical trials).
7. Adverse reactions caused by previous anti-tumor treatments did not recover to grade 1 or below (hair loss and peripheral neuropathy did not recover to grade 2 or below).
8. Active infection or unexplained fever\> 38.5°C occurred within 2 weeks before the first administration (according to the judgment of the investigator, the subject can be included in the group for fever caused by the tumor).
9. Various chronic active infections, such as hepatitis B virus (evidence of hepatitis activity such as HBV-DNA ≥104 copies/ml or 2000IU/ml), hepatitis C and HIV.
10. Patients with elevated serum troponin T or I (above the normal limit specified by the research center).
11. Pregnant or lactating (lactating) women, where pregnancy is defined as the state of a woman after conception until the end of pregnancy, and the result of a serum β-human chorionic gonadotropin (β-hCG) laboratory test is confirmed to be positive.
12. Any of the following cardiac standards: the average QTcF calculated according to Fridericia's formula during the rest period of the screening period \[QTcF = QT/(RR1/3), RR is the standardized heart rate value, obtained by dividing 60 by the heart rate\]: male\> 450 milliseconds , Female\> 470 milliseconds; any clinically important abnormalities in the rhythm, conduction or morphology of the resting electrocardiogram (ECG) (for example, complete left bundle branch block, third degree heart block, second degree heart block); Congenital long QT syndrome or family history of long QT syndrome.
13. According to the investigator's judgment, patients who have not fully recovered after surgery, patients whose wounds are in an active healing stage, patients who underwent major surgery within 28 days before the start of the study, and patients who underwent minor surgery within 14 days before the start of the study.
14. Severe and uncontrollable accompanying diseases that may affect protocol compliance or interfere with the interpretation of results, including active opportunistic infections or advanced (severe) infections, and diabetes that cannot be controlled after adequate clinical anti-hyperglycemia treatment according to guidelines , Uncontrollable hypertension, cardiovascular disease (Class III or IV heart failure as defined by the New York Heart Association classification, heart block above II, congestive heart failure (CHF), myocardial infarction in the past 6 months , Unstable arrhythmia or unstable angina, cerebral infarction within 3 months, etc.) or lung disease (history of interstitial pneumonia, obstructive lung disease and symptomatic bronchospasm).
15. Any other situation that the researcher considers inappropriate to participate in clinical research.

Primary outcomes:
measure: ORR
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: PFS
timeFrame: through study completion, an average of 1 year
measure: DCR
timeFrame: through study completion, an average of 1 year
measure: OS
timeFrame: through study completion, an average of 1 year
measure: DOR
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xianjun MD Yu, PhD
role: PRINCIPAL_INVESTIGATOR
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