Clinical trial NCT05810792: Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer
Official title: A Phase I/II Trial of Peri- and Postoperative Treatment With Histamine Dihydrochloride and Low-dose Interleukin-2 in Patients With Primary Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Pancreatic Cancer
Surgery
Metastasis
Immunosuppression
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
First posted: 2023-04-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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

Brief 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.


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.

Primary outcomes:
measure: Incidence and severity of Treatment-Emergent Adverse Events as assessed by NCI-CTCAE
timeFrame: When the first 14 patients have undergone one full 3-week cycle with HDC/IL-2 (approximately 18 months after trial start)
Secondary outcomes:
measure: Overall survival
timeFrame: 24 months
measure: Disease free survival
timeFrame: 24 months
measure: Changes in Natural killer cell subsets in blood
timeFrame: Change from pre-surgical levels to levels during the post-surgical week
measure: Changes in T cell subsets in blood
timeFrame: Change from pre-surgical levels to levels during the post-surgical week
measure: Changes in Myeloid cell populations
timeFrame: Change from pre-surgical levels to levels during the post-surgical week
measure: Tumor infiltrating lymphocytes and tumor infiltrating myeloid cells
timeFrame: immediately after the surgery
measure: Carbohydrate antigen 19-9
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Västra Götalandsregionen, Sahlgrenska University Hospital
name: Andreas Muth
role: STUDY_DIRECTOR
References: