Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer

NCT ID: NCT05810792

Last Updated: 2023-11-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2028-04-01

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.

Conditions

Pancreatic Cancer; Surgery; Metastasis; Immunosuppression

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients receiving immunomodulating treatment

Group Type: EXPERIMENTAL

Histamine Dihydrochloride (HDC)

Intervention Type: DRUG

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.

Interleukin-2 (IL-2)

Intervention Type: DRUG

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).

Interventions

Histamine Dihydrochloride (HDC)

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.

Intervention Type: DRUG

Interleukin-2 (IL-2)

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).

Intervention Type: DRUG

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sahlgrenska University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Svein Olav Bratlie

Senior surgeon, Dr Med, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andreas Muth

Role: STUDY_DIRECTOR

Västra Götalandsregionen, Sahlgrenska University Hospital

Central Contacts

Svein Olav Bratlie

Role: CONTACT

svein.olav.bratlie@vgregion.se

+46313428218

Other Identifiers

PANCEP-1, April 1 2020

Identifier Type: -

Identifier Source: org_study_id