Examining Safety, Efficacy and Feasibility of Preoperative Propranolol in Patients With PDAC.

NCT06145074 | Recruiting Phase 2

• 1 other identifier: EU CT 2023-506553-37-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The IMPULS trial is a randomized, triple-blinded, placebo controlled, single center, pilot trial examining the efficacy and safety of preoperative propranolol in patients scheduled for pancreatic cancer surgery. The study is conducted as a type 1 hybrid efficacy-implementation trial of 30 patients. This study is designed to provide pilot data for a future larger perioperative study of propranolol with the aim of improving outcomes for pancreatic cancer surgery. In total, 30 participants will be allocated in a 1:1 ratio with 15 participants enrolled in each trial arm (propranolol vs. placebo). Participants will be allocated to either 40 mg propranolol twice daily or placebo twice daily in 10 days prior to planned surgery. Primary outcomes: Evaluating the efficacy of preoperative propranolol on anxiety and in pro-tumorigenic changes (e.g., in the tumor tissue and in blood samples) in patients undergoing surgery for pancreatic cancer. Furthermore, to obtain follow up data (e.g., 90-day mortality, postoperative complications etc. on the patients receiving propranolol versus placebo). Heart rate variability among the participants will also be examined. Secondary: Examining the safety and tolerability of 40 mg preoperative propranolol twice daily in patients undergoing surgery for pancreatic cancer. Tertiary: Evaluating the feasibility and implementation of the trial (using the APEASE framework). This will help identify barriers and enablers to a future larger study. Short-time propranolol treatment is considered safe with a mild and manageable safety-profile. Risk-management, mitigations and guidelines to ensure patient safety is included in the protocol. Since this clinical trial is exploratory in nature, no sample-size calculation is performed.

Conditions

Pancreatic Cancer; Surgery

Keywords

Propranolol; Beta-Blockers; PDAC; Pancreatic Cancer

Outcome Measures

Primary Outcomes (18)

• Preoperative anxiety

  Assessed through the Hamilton Anxiety Rating Scale (HAMA) questionnaire

  Obtained preoperatively at baseline (immediately after inclusion) and immediately after intervention (before surgery)

• Preoperative anxiety and depression

  Assessed through the Hospital Anxiety and Depression Scale (HADS) questionnaire

  Obtained preoperatively at baseline (immediately after inclusion) and immediately after intervention (before surgery)

• Preoperative quality of life

  Preoperative quality of life assessed through the quality of life questionnaire.

  Obtained preoperatively at baseline (immediately after inclusion) and immediately after intervention (before surgery)

• Density and subtypes of tumor-infiltrating lymphocytes in the tumor microenvironment.

  Histopathological assessment of the density and subtypes of tumor-infiltrating lymphocytes. Immunohistochemistry technique will be used.

  Through study completion. At latest within 1 year from last participant completes trial.

• Desmoplasia in the tumor microenvironment.

  Histopathological assessment of desmoplasia in the tumor microenvironment. Immunohistochemistry technique will be used.

  Through study completion. At latest within 1 year from last participant completes trial.

• Neural markers in the tumor microenvironment.

  Histopathological assessment of neural marker expression (e.g., NGF, BDNF, tyrosin hydroxylase) Immunohistochemistry technique will be used.

  Through study completion. At latest within 1 year from last participant completes trial.

• Adrenergic receptor (ADRB1&ADRB2) expression in the tumor microenvironment.

  Histopathological assessment of the expression of adrenergic receptors (ADRB1 and ADRB2). Immunohistochemistry technique will be used for this purpose.

  Through study completion. At latest within 1 year from last participant completes trial.

• Spatial distribution of immune cells in the tumor microenvironment.

  Spatial distribution of immune cells in the tumor microenvironment using Immunohistochemistry technique and NanoString GeoMx techniques will be used for this purpose.

  Through study completion. At latest within 1 year from last participant completes trial.

• Immune cells and subtypes in blood samples

  Assessing the number and subsets of immune cells in the obtained blood samples before and after propranolol treatment and between the two arms (propranolol versus placebo). This will be examined through FlowCytometry.

  Through study completion. At latest within 1 year from last participant completes trial.

• Circulating tumor cells before and after intervention in blood samples.

  Assessment of circulating tumor cells in blood samples before and after intervention.

  Through study completion. At latest within 1 year from last participant completes trial.

• RNA-level gene expression in blood samples.

  RNA-level expression of genes related to immune-surveillance through NanoString nCounter technique.

  Through study completion. At latest within 1 year from last participant completes trial.

• Heart rate variability in both trial arms

  Examining differences in heart rate variability among participants and between intervention and comparator group.

  Through study completion, an average of 1 year.

• Postoperative complications

  Assessment of postoperative complications based on the Clavien-Dindo Score (CD) ranging from I to V, where I is any decline from normal postoperative course and V is death of patient.

  After participant finishes trial and when last follow up (5 years from surgery) date is due.

• Survival 30-days after surgery

  Assessment of survival 30 days after surgery.

  After participant finishes trial and when last follow up (5 years from surgery) date is due.

• Survival 90-days after surgery

  Assessment of survival 90 days after surgery.

  After participant finishes trial and when last follow up (5 years from surgery) date is due.

• Overall survival 1-year after surgery

  Assessment of overall surival 1-year after surgery

  After participant finishes trial and when last follow up (5 years from surgery) date is due.

• Overall survival 3-years after surgery

  Assessment of overall survival 3-years after surgery

  After participant finishes trial and when last follow up (5 years from surgery) date is due.

• Overall survival 5-years after surgery

  Assessment of overall survival 5-years after surgery

  After participant finishes trial and when last follow up (5 years from surgery) date is due.

Secondary Outcomes (2)

• Safety of 40 mg propranolol twice daily on blood pressure.

  Through study completion, within 14 days after surgery.

• Safety of 40 mg propranolol twice daily on heart rate.

  Through study completion, within 14 days after surgery.

Other Outcomes (1)

• Feasibility of implementing preoperative propranolol in the preoperative setting for patients with pancreatic cancer using the APEASE framework.

  Within 1 year from end of the trial.

Study Arms (2)

Propranolol

EXPERIMENTAL

Propranolol will be administered 40 mg twice daily (morning and evening) in 10 days prior to surgery for pancreatic cancer

Drug: Propranolol

Placebo

PLACEBO COMPARATOR

Placebo will be administered twice daily (morning and evening) in 10 days prior to surgery for pancreatic cancer.

Drug: Placebo

Interventions

Propranolol DRUG

Oral administration.

Also known as: Inderal, Propal

Propranolol

Placebo DRUG

Oral administration.

Also known as: Inactive drug

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with suspected surgically resectable pancreatic cancer
• Indication for surgical treatment with curative intend.
• Provide written informed consent.
• Patients minimum 18 years old.
• Women of childbearing potential (WOCBP) are defined as women ranging from the period of menarche till the post-menopausal period, unless permanently sterile (e.g., hysterectomy, bilateral salpingectomy and bilateral oophorectomy). Post-menopause is defined as no menses for 12 months without an alternative medical cause.
• WOCBP should use a secure and highly effective birth control (as stated in the "Recommendations related to contraception and pregnancy testing in clinical trials", version 1.1., section 4.1, from the Clinical Trials Facilitation and Coordination Group) during the entire period of the trial. In cases of uncertainty regarding pregnancy, additional pregnancy testing either as highly sensitive serum or urine pregnancy test can be used.

You may not qualify if:

• Patients with:
• Chronic hypotension, systolic blood pressure \< 100 mg Hg for women and \< 110 mg Hg for men.
• Bradycardia, pulse \< 50 beats per minute.
• Asthma or chronic obstructive lung disease
• Heart insufficiency with affected (\< 50 %) left ventricle ejection fraction (LVEF), treated or untreated.
• Kidney insufficiency, defined as eGFR \< 20 ml/min.
• Liver insufficiency defined as chronically high liver enzymes or known chronic liver disease (e.g., hepatitis, steatosis, cirrhosis).
• Cor pulmonale
• Cardiogenic shock
• Severe peripheral circulatory disorders
• Known or newly diagnosed current metabolic acidosis (e.g., in recent analysis of arterial puncture).
• Known hypersensitivity to propranolol or to one or more of the excipients.
• Currently untreated pheochromocytoma.
• History of Prinzmetals angina.
• History of sick sinus syndrome or atrioventricular block.

Sponsors & Collaborators

• Zealand University Hospital: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (2)

Department of Surgical Gastroenterology

Copenhagen, 2200, Denmark

RECRUITING

Ismail Gögenur

Køge, 4600, Denmark

NOT YET RECRUITING

Related Links

• Drug Information - Propranolol

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Ismail Gögenur, Professor

  Center for Surgical Science, Zealand University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ismail Gögenur, Professor

CONTACT

+4547323181; igo@regionsjaelland.dk

Adile Orhan, MD

CONTACT

+4560807762; aor@regionsjaelland.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: November 22, 2023
• Study Start: March 20, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2035
• Last Updated: March 28, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)