Clinical trial NCT06241352: Statin Addition to Chemotherapy for Advanced Pancreatic Cancer
Official title: A Prospective Clinical Trial of Statin Addition to Chemotherapy for Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Pancreatic Cancer
Keywords: advanced pancreatic cancer
statin
chemotherapy resistance
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
First posted: 2024-02-05
Enrollment: 42
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 results of previous studies conducted by our team have revealed that the use of statins can more effectively hinder the growth of drug-resistant pancreatic cancer cells. The primary objective of this study was to investigate the role of statins in treating pancreatic cancer by assessing the safety and therapeutic impact of combining chemotherapy with statins in patients with advanced pancreatic cancer.

Detailed description: The poor prognosis of pancreatic cancer is not just because of the high malignancy of the tumor itself, but also its poor response to chemotherapy. Gemcitabine and fluorouracil are the primary drugs utilized in pancreatic cancer treatment, and combination chemotherapy predominantly revolves around these two drugs. Nevertheless, findings from clinical studies reveal that approximately one-third of pancreatic cancer patients display resistance to chemotherapy, with the majority of the remaining patients eventually developing secondary resistance within six months following treatment. Consequently, chemotherapy resistance constitutes a significant factor contributing to the poor prognosis of pancreatic cancer patients.

Our research team established a biobank containing over 300 pancreatic cancer organoids. Using high-throughput drug sensitivity detection techniques, the investigators assessed the sensitivity of 177 pancreatic cancer organoids to five commonly used chemotherapeutics and 84 tumor-related drugs or regimens. The findings suggest that pancreatic cancer organoids that are generally resistant to chemotherapy drugs exhibit sensitivity to statins. These findings indicate that combining chemotherapy with statins may enhance the therapeutic effect for pancreatic cancer patients. Previous studies have also reported the potential therapeutic effects of statins in colorectal, lung and breast cancer.

In summary, chemotherapy resistance is a significant factor contributing to the poor prognosis of pancreatic cancer. Building on previous research conducted by our team, this study aims to investigate the role of statins in pancreatic cancer through a single-arm clinical trial, with the goal to investigate the role of statins in treating pancreatic cancer.

Eligibility criteria: Inclusion Criteria:

* Age≥18 years old and ≤80 years old.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
* Histologically or cytologically confirmed local advanced/metastatic pancreas adenocarcinoma.
* Imaging studies confirmed the diagnosis of locally advanced or metastatic pancreatic cancer patients.
* The patients were in the plateau stage after chemotherapy, as indicated by the CA19-9 values (with CA19-9 negative patients referenced against CEA or CA-125) fluctuating by less than 20% over an interval of more than 3 weeks.
* Life expectancy of greater than 90 days, as judged by the investigator.
* Routine blood test: absolute neutrophil count\>1500/mm3, platelet\>100000/ mm3.
* Normal liver function: serum total bilirubin≤2.0mg/dl, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3 times of the upper limit of normal value.
* Normal kidney function: serum creatinine\<1.5 times of the upper limit of normal value or creatinine clearance rate\>45ml/min.
* No severe comorbidities.

Exclusion Criteria:

* Patients with poor condition can not tolerate chemotherapy.
* Patients who have previously taken lipid-lowering drugs (such as statins, fibrates, ezetimibe, or PCSK9 inhibitors).
* Patients who are taking warfarin, verapamil, clopidogrel, digoxin, amiodarone, etc.
* Impaired organ functions: heart failure (New York Heart Association III- IV), coronary heart disease, myocardial infarction within 6 months, severe cardiac arrhythmia and respiratory failure.
* Patients diagnosed with other cancer within 5 years.
* Patients who are pregnant or breastfeeding.
* Patients enrolled in other clinical trials or incompliant of regular follow up.
* Patients who did not provide an informed consent.

Primary outcomes:
measure: Decrease rate of CA19-9 (with CA19-9 negative patients referenced against CEA or CA-125)
timeFrame: 1-2 month
Secondary outcomes:
measure: Event-free Survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 2 years
measure: Disease control rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Changhai Hospital, Shanghai, China
name: Gang Jin, MD
role: PRINCIPAL_INVESTIGATOR
References: