Phase I/II Evaluation of Perioperative Histamine Dihydrochloride and Low-Dose Aldesleukin in Resectable Pancreatic Cancer Patients
- Trial ID
- 2023-506979-10-00
- Sponsor
- Vaestra Goetalandsregionen
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase I/II trial is to assess the frequency and extent of **adverse events** associated with peri- and postoperative treatment using histamine dihydrochloride and low-dose interleukin-2 in patients with primary resectable **pancreatic cancer**. This evaluation is clinically relevant as it aims to determine the safety profile of the treatment regimen, which is crucial for understanding its potential risks and benefits in this patient population.
Secondary objectives include:
- Determining the clinical efficacy of peri- and postoperative treatment with HDC/IL-2 in patients with primary resectable pancreatic cancer, using matched, contemporary control patients as the comparator.
- Investigating the efficacy of peri- and postoperative therapy with HDC/IL-2 versus control patients in the IPEP study on certain biomarkers relating to inflammation and/or immune responses.
Participants
The clinical trial involves participants diagnosed with **pancreatic cancer**, specifically targeting individuals with primary resectable pancreatic or periampullary cancer, including pancreatic ductal adenocarcinoma, ampullary carcinoma, and cholangiocarcinoma. The study population comprises both male and female subjects aged over 18 years, who are deemed fit for pancreatic surgery by a surgeon's evaluation. Participants must have radiologic and/or cytologic confirmation of their condition. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **phase I/II** study to evaluate the safety and tolerability of peri- and postoperative treatment with **histamine dihydrochloride** and low-dose **aldesleukin** in patients with primary resectable **pancreatic cancer**. The trial employs a randomized, double-blind, controlled methodology to ensure the reliability and validity of the results. The estimated duration of the trial is from April 2024 to January 2029, with participant involvement expected to last until the end of the study or until early termination criteria are met.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, fitness for pancreatic surgery, and confirmation of resectable pancreatic or periampullary cancer. Following the screening, participants will be randomized to receive either the investigational treatment or a control. Regular follow-up visits will be scheduled to monitor the safety and efficacy of the treatment, with adverse events being assessed and graded according to the NCI-CTCAE, version 5.0. The primary endpoint focuses on the safety and tolerability of the treatment, while secondary endpoints include progression-free survival, overall survival, and various biomarker analyses.
The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial aims to provide comprehensive data on the safety profile of the treatment regimen, contributing valuable insights into its potential therapeutic benefits for patients with pancreatic cancer.
Treatment
The clinical trial involves the administration of **PROLEUKIN®**, which contains the active substance **aldesleukin**. This medication is provided as a powder for solution for injection or infusion, with a concentration of 18 x 106 IU. The pharmaceutical form is a solution for injection or infusion, and it is administered subcutaneously. The frequency and specific dosing schedule are determined by the study protocol, and participant compliance is monitored throughout the trial. Aldesleukin is a protein-based therapeutic agent, classified under the ATC code L03AC01, and is manufactured by Clinigen Healthcare Ltd.
Another experimental medication used in the trial is **Ceplene**, which contains the active substance **histamine dihydrochloride**. This medication is formulated as a solution for injection, with a concentration of 0.5 mg/0.5 mL. It is also administered subcutaneously. The administration schedule and dosage are specified in the study protocol, with adherence to the regimen being closely monitored. Histamine dihydrochloride is a chemically derived substance, and the product is manufactured by Laboratoires Delbert. The ATC classification for this substance is L03AX14.
In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The primary objective of the trial is to assess the frequency and extent of adverse events associated with the therapy. The trial is designed to evaluate the safety and potential therapeutic effects of the combination of these two experimental medications in patients with primary resectable pancreatic cancer.
Efficacy
Efficacy in this clinical trial will be assessed through several secondary endpoints, focusing on both survival outcomes and biomarker analysis. The secondary efficacy variables include **progression-free survival** and **overall survival**. These parameters will be measured to evaluate the effectiveness of the treatment regimen in patients with primary resectable pancreatic cancer.
Additionally, the trial will involve comprehensive biomarker analysis to further assess efficacy. This includes evaluating natural killer (NK) cell subsets in blood, such as immature (CD16-) and cytotoxic (CD16+) subsets, along with activation markers and natural cytotoxicity receptors like NKp30, NKp46, and NKG2D. T cell subsets, including CD4+/25 regulatory T cells and various CD8+ T cell types, will also be analyzed. Myeloid cell populations, including granulocytes, monocytes, myeloid-derived suppressor cells (MDSC), dendritic cells, and related immune biomarkers such as PD-L1 and PD-L2, will be assessed. Serum levels of CA 19-9, cytokines, chemokines, and other soluble mediators of inflammation will be measured. The amount of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating myeloid cells will also be evaluated.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution.
- Patient is a male or female age >18
- By the surgeons evaluation fit for pancreatic surgery
- Subjects must have radiologic, and/or cytologic confirmation of primary resectable pancreatic or periampullary cancer. Pancreatic ductal adenocarcinoma, ampullary carcinoma and cholangiocarcinoma are the most common forms, but also other rare forms of pancreatic and periampullary cancer may be included.
Exclusion Criteria
- Class III or IV cardiac disease, hypotension or severe hypertension, vasomotor instability, serious or uncontrolled cardiac dysrhythmias (including ventricular arrhythmias) at any time, acute myocardial infarction within the past 6 months, active uncontrolled angina pectoris or symptomatic arteriosclerotic blood vessel disease.
- History of uncontrolled seizures, severe central nervous system disorders, or psychiatric disability thought to be clinically significant in the opinion of the Investigator and adversely affecting compliance to protocol.
- Ongoing treatment with immunomodulating medication, i.e. corticosteroids.
- Ongoing active peptic ulcer.
- Ongoing asthma.
- Any other condition or symptoms preventing the patient from entering the study, according to the PI's judgement.
- A woman of childbearing potential (WOCBP) must agree to comply with using an effective contraceptive method for the duration of the treatment (a WOCBP is a sexually mature woman who is not surgically sterile or has not been naturally postmenopausal for at least 12 consecutive months). Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. Local laws and regulations may require use of alternative and/or additional contraception methods. One of the highly effective methods of contraception listed below is required during study duration and until the end of relevant systemic exposure, defined as 5 months after the end of study treatment.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Sweden | Recruiting | 01 Apr 2024 | 50 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PROLEUKIN® 18 x 106 IU Powder for solution for injection or infusion | Test | POWDER FOR SOLUTION FOR INJECTION OR INFUSION | SUBCUTANEOUS | — | — | PRD7266563 |
Ceplene 0.5 mg/0.5 mL solution for injection | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS | — | — | PRD9895375 |