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Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer (PANCEP-1)

Primary Purpose

Pancreatic Cancer, Surgery, Metastasis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Histamine Dihydrochloride (HDC)
Interleukin-2 (IL-2)
Sponsored by
Sahlgrenska University Hospital, Sweden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. Subject is a male or female age >18 By the surgeon´s evaluation fit for pancreatic surgery Subjects must have radiologic, and or cytologic confirmation of primary pancreatic cancer Exclusion Criteria (any of the following): 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. 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. 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Patients receiving immunomodulating treatment

    Arm Description

    Outcomes

    Primary Outcome Measures

    Incidence and severity of Treatment-Emergent Adverse Events as assessed by NCI-CTCAE
    Incidence and severity grade of adverse events occuring during and after treatment will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

    Secondary Outcome Measures

    Overall survival
    Comparing matched historical controls from national registry
    Disease free survival
    Comparing matched historical controls from national registry
    Changes in Natural killer cell subsets in blood
    Changes in NK cell number and expression of activation markers during surgery
    Changes in T cell subsets in blood
    Changes in T cell number and expression of activation markers during surgery
    Changes in Myeloid cell populations
    Changes in myeloid cell number and markers of activation and inhibition
    Tumor infiltrating lymphocytes and tumor infiltrating myeloid cells
    Tumor pieces removed during surgery will be assessed for immune populations
    Carbohydrate antigen 19-9
    Serum CA 19-9 levels are monitored as a biomarker for disease recurrance

    Full Information

    First Posted
    March 7, 2023
    Last Updated
    March 31, 2023
    Sponsor
    Sahlgrenska University Hospital, Sweden
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05810792
    Brief Title
    Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer
    Acronym
    PANCEP-1
    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

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    September 2025 (Anticipated)
    Study Completion Date
    December 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Sahlgrenska University Hospital, Sweden

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pancreatic Cancer, Surgery, Metastasis, Immunosuppression

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    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).
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Patients receiving immunomodulating treatment
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Histamine Dihydrochloride (HDC)
    Intervention 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.
    Intervention Type
    Drug
    Intervention Name(s)
    Interleukin-2 (IL-2)
    Intervention 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).
    Primary Outcome Measure Information:
    Title
    Incidence and severity of Treatment-Emergent Adverse Events as assessed by NCI-CTCAE
    Description
    Incidence and severity grade of adverse events occuring during and after treatment will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
    Time Frame
    When the first 14 patients have undergone one full 3-week cycle with HDC/IL-2 (approximately 18 months after trial start)
    Secondary Outcome Measure Information:
    Title
    Overall survival
    Description
    Comparing matched historical controls from national registry
    Time Frame
    24 months
    Title
    Disease free survival
    Description
    Comparing matched historical controls from national registry
    Time Frame
    24 months
    Title
    Changes in Natural killer cell subsets in blood
    Description
    Changes in NK cell number and expression of activation markers during surgery
    Time Frame
    Change from pre-surgical levels to levels during the post-surgical week
    Title
    Changes in T cell subsets in blood
    Description
    Changes in T cell number and expression of activation markers during surgery
    Time Frame
    Change from pre-surgical levels to levels during the post-surgical week
    Title
    Changes in Myeloid cell populations
    Description
    Changes in myeloid cell number and markers of activation and inhibition
    Time Frame
    Change from pre-surgical levels to levels during the post-surgical week
    Title
    Tumor infiltrating lymphocytes and tumor infiltrating myeloid cells
    Description
    Tumor pieces removed during surgery will be assessed for immune populations
    Time Frame
    immediately after the surgery
    Title
    Carbohydrate antigen 19-9
    Description
    Serum CA 19-9 levels are monitored as a biomarker for disease recurrance
    Time Frame
    12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Subjects must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. Subject is a male or female age >18 By the surgeon´s evaluation fit for pancreatic surgery Subjects must have radiologic, and or cytologic confirmation of primary pancreatic cancer Exclusion Criteria (any of the following): 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. 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. 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Svein Olav Bratlie
    Phone
    +46313428218
    Email
    svein.olav.bratlie@vgregion.se
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Erik Johnsson
    Organizational Affiliation
    Västra Götalandsregionen, Sahlgrenska University Hospital
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer

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