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NCT Number: NCT05810792

Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer

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.

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Key information

Conditions

Pancreatic Cancer Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Immunosuppression Metastasis Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Pancreatic Diseases Pancreatic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Surgery

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Histamine Dihydrochloride (HDC)

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)

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).

Primary outcomes

  1. Incidence and severity of Treatment-Emergent Adverse Events as assessed by NCI-CTCAE

    Time frame: When the first 14 patients have undergone one full 3-week cycle with HDC/IL-2 (approximately 18 months after trial start)

    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 outcomes

  1. Overall survival

    Time frame: 24 months

    Comparing matched historical controls from national registry

  2. Disease free survival

    Time frame: 24 months

    Comparing matched historical controls from national registry

  3. Changes in Natural killer cell subsets in blood

    Time frame: Change from pre-surgical levels to levels during the post-surgical week

    Changes in NK cell number and expression of activation markers during surgery

  4. Changes in T cell subsets in blood

    Time frame: Change from pre-surgical levels to levels during the post-surgical week

    Changes in T cell number and expression of activation markers during surgery

  5. Changes in Myeloid cell populations

    Time frame: Change from pre-surgical levels to levels during the post-surgical week

    Changes in myeloid cell number and markers of activation and inhibition

  6. Tumor infiltrating lymphocytes and tumor infiltrating myeloid cells

    Time frame: immediately after the surgery

    Tumor pieces removed during surgery will be assessed for immune populations

  7. Carbohydrate antigen 19-9

    Time frame: 12 months

    Serum CA 19-9 levels are monitored as a biomarker for disease recurrance

Study contacts

Contact information is provided by the study sponsor or research team.

Svein Olav Bratlie

CONTACT

[email protected]

+46313428218

Sponsors and collaborators

Lead sponsor

Sahlgrenska University Hospital

Other

Registry information

Official study 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

Acronym: PANCEP-1

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Apr 12, 2023
Registry last updated
Nov 22, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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