Pancreatic CancerPhase 2PANCEP-1NCT05810792
Histamine Dihydrochloride and Interleukin-2 in Primary Resectable Pancreatic Cancer
A Phase 2 study testing Histamine Dihydrochloride (HDC) and Interleukin-2 (IL-2) in people with Pancreatic Cancer and Surgery, run by Sahlgrenska University Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Surgery, Metastasis
- What is being tested?
- Histamine Dihydrochloride (HDC) and Interleukin-2 (IL-2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2024to 1 Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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
- Being tested
- Histamine Dihydrochloride (HDC), Interleukin-2 (IL-2)
- Medical subject headings
- Pancreatic Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
| Study group | Role | What they receive |
|---|---|---|
| Patients receiving immunomodulating treatment | Experimental | Not described Receives: Drug: Histamine Dihydrochloride (HDC); Drug: Interleukin-2 (IL-2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: When the first 14 patients have undergone one full 3-week cycle with HDC/IL-2 (approximately 18 months after trial start)
Secondary outcomes (7)
Overall survival
Comparing matched historical controls from national registry
Measured: 24 months
Disease free survival
Comparing matched historical controls from national registry
Measured: 24 months
Changes in Natural killer cell subsets in blood
Changes in NK cell number and expression of activation markers during surgery
Measured: Change from pre-surgical levels to levels during the post-surgical week
Changes in T cell subsets in blood
Changes in T cell number and expression of activation markers during surgery
Measured: Change from pre-surgical levels to levels during the post-surgical week
Changes in Myeloid cell populations
Changes in myeloid cell number and markers of activation and inhibition
Measured: Change from pre-surgical levels to levels during the post-surgical week
Tumor infiltrating lymphocytes and tumor infiltrating myeloid cells
Tumor pieces removed during surgery will be assessed for immune populations
Measured: immediately after the surgery
Carbohydrate antigen 19-9
Serum CA 19-9 levels are monitored as a biomarker for disease recurrance
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2023
- Study start1 Apr 2024 (estimated)
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Svein Olav Bratlie, Sahlgrenska University Hospital
- Investigators
- Andreas Muth, Study director, Västra Götalandsregionen, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05810792
- Sponsor's protocol ID
- PANCEP-1, April 1 2020
- Acronym
- PANCEP-1
- Status last verified
- Nov 2023
- First submitted
- 7 Mar 2023
- Last updated
- 22 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05810792
- Acronym / sponsor ID
- PANCEP-1 / PANCEP-1, April 1 2020
- Conditions
- Pancreatic Cancer, Surgery, Metastasis, Immunosuppression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Study start
- 1 Apr 2024 (estimated)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 12 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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).
| Arm | Type | Receives |
|---|---|---|
| Patients receiving immunomodulating treatment | Experimental | Drug: Histamine Dihydrochloride (HDC), Drug: Interleukin-2 (IL-2) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Patients receiving immunomodulating treatment |
| 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). | Drug | Patients receiving immunomodulating treatment |
Primary outcome
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.
7 secondary outcomes
Overall survival
Time frame: 24 months
Disease free survival
Time frame: 24 months
Changes in Natural killer cell subsets in blood
Time frame: Change from pre-surgical levels to levels during the post-surgical week
Changes in T cell subsets in blood
Time frame: Change from pre-surgical levels to levels during the post-surgical week
Changes in Myeloid cell populations
Time frame: Change from pre-surgical levels to levels during the post-surgical week
Tumor infiltrating lymphocytes and tumor infiltrating myeloid cells
Time frame: immediately after the surgery
Carbohydrate antigen 19-9
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andreas Muth study director
Västra Götalandsregionen, Sahlgrenska University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Histamine Dihydrochloride (HDC) and Interleukin-2 (IL-2) in people with Pancreatic Cancer and Surgery, run by Sahlgrenska University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Svein Olav Bratlie (+46313428218, svein.olav.bratlie@vgregion.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.