Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer

Trial Title: Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer

NCT ID: NCT05810792

Condition: Pancreatic Cancer
Surgery
Metastasis
Immunosuppression

Conditions: Official terms:
Pancreatic Neoplasms
Interleukin-2
Histamine
Histamine phosphate

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: This is a single center, open-label study in subjects with resectable pancreatic cancer. Eligible subjects will be offered treatment with histamine dihydrochloride and low-dose interleukin-2. Secondary endpoints comparing matched historical controls (DFS, OS).

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Histamine Dihydrochloride (HDC)
Description: HDC is administrated in combination with IL-2 as peri- and post-operative treatment in patients undergoing surgery. 0.5 mg HDC is administered twice daily by subcutaneous injections 1 to 3 minutes after each IL-2 injection during three 3 week cycles, with 3-week resting periods inbetween. The first treatment cycle is initated 2 weeks prior to surgery, with an additional 2-3 days rest period during the surgical procedure, before the third treatment week is initiated.
Arm group label: Patients receiving immunomodulating treatment

Intervention type: Drug
Intervention name: Interleukin-2 (IL-2)
Description: IL-2 is administrated in combination with HDC during three 3 week cycles as peri- and post-operative treatment in patients undergoing surgery. IL-2 is administered twice daily as a subcutaneous injection 1 to 3 minutes prior to the administration of histamine dihydrochloride; each dose of IL-2 is 16,400 IU/kg (1µg/kg).
Arm group label: Patients receiving immunomodulating treatment

Summary: A key aspect of the trial is that functions of anti-neoplastic T cells and natural killer (NK) cells, may be inhibited by immunosuppressive signals from myeloid cells, in particular reactive oxygen species (ROS) produced by several subsets of myeloid cells. In cancer, such immunosuppressive cells are commonly denoted myeloid-derived suppressor cells (MDSCs), which are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive ROS via myeloid cell NADPH oxidase (NOX2). The presence of MDSCs within or adjacent to tumor tissue is assumed to facilitate the growth and spread of tumors and may also dampen the efficacy of cancer immunotherapies. The underlying hypothesis for this clinical trial is the administration of HDC/IL-2 will reduce surgery-induced inflammation and reduce metastasis. A phase I/II open label, single-center study of the safety, tolerability, and efficacy of peri- and postoperative therapy with histamine dihydrochloride and low-dose interleukin-2 treatment in subjects with primary pancreatic cancer.To assess the frequency and extent of adverse events associated with low dose interleukin-2 and histamine dihydrochloride when used as perioperative therapy.To determine progression free survival and overall survival following surgery, and compare with matched historical controls from the Swedish Cancer Registry.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Subjects must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. 2. Subject is a male or female age >18 3. By the surgeon´s evaluation fit for pancreatic surgery 4. Subjects must have radiologic, and or cytologic confirmation of primary pancreatic cancer Exclusion Criteria (any of the following): 1. 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 peripheral blood vessel disease. 2. 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. 3. Any other condition or symptoms preventing the patient from entering the study, according to the PI's judgement. 4. 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: April 1, 2024

Completion date: April 1, 2028

Lead sponsor:
Agency: Sahlgrenska University Hospital, Sweden
Agency class: Other

Source: Sahlgrenska University Hospital, Sweden

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05810792