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Bethanechol Prior to Pancreatic Surgery

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ClinicalTrials.gov Identifier: NCT03572283
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
Susan E. Bates, Columbia University

Brief Summary:

The primary objective of this study is to assess the impact of bethanechol therapy on tumor activity by looking at biomarkers of proliferation, inflammation, and stem cell markers in post-treatment specimens compared to pre-treatment specimens and compared to other patients who were not treated with bethanechol prior to surgery. The investigators hypothesize that treatment with bethanechol will alter nerve conduction within tumors by stimulating the parasympathetic nervous system and reduce tumor proliferation, reduce macrophage activation, reduce tumor necrosis factor (TNF) alpha, and decrease human cluster of differentiation 44 (CD44) protein cancer stem cells.

The safety objective is to assess the safety and tolerability of short course bethanechol prior to surgery and the impact of this treatment on immediate surgical outcomes. The investigators will assess all treatment-related toxicities with an emphasis on GI side effects and evaluate the impact of therapy on surgical delays or immediate post-op complications. All subjects will be contacted 1 week after beginning therapy to assess toxicity including GI specific toxicity and followed for safety for 30 days following completion of study medication. The investigators hypothesize that treatment for a minimum of 1 week will be tolerable in this selected patient population and will not interfere with progression to surgery or lead to increased surgical complications.


Condition or disease Intervention/treatment Phase
Pancreas Cancer Drug: Bethanechol Early Phase 1

Detailed Description:

Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult cancers and, unlike other common cancers, annual deaths from PDA are rising. During the year 2017, it was estimated that 53,670 people would be diagnosed with PDA and approximately 43,090 people would die in the U.S. Despite recent advances, cytotoxic chemotherapy for PDA has been disappointing with response rates of 20-30% for the most active regimens and little activity for targeted therapies. Even among the small subset of patients who are suitable for surgical resection at the time of diagnosis, complete resection is followed by recurrence in >90% of patients without further systemic therapy, with a median time to recurrence of 6.9 months. Thus all PDA patients require systemic chemotherapy and more effective regimens are urgently needed.

The purpose of this study is to determine whether the drug, bethanechol, could potentially be used in combination with surgery to decrease the chance of cancer coming back after it is removed. Bethanechol is a medication that is approved by the FDA and regulates the parasympathetic nervous system. It is used to treat dry mouth and for patients who have difficulty urinating. It has been used to manage the side effects of chemotherapy drugs. The investigators planned this study in pancreatic cancer because animal models have shown that treatment with bethanechol can inhibit cancer growth and spread. People with pancreatic cancer localized to a small area usually undergo surgery to remove the tumor. The study is designed to investigate that the medication is easy to tolerate and that it shows signs of slowing cancer cell growth.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Phase 0 study to assess the impact of bethanechol on pancreatic cancer biomarkers
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Phase 1 Window of Opportunity Study of Parasympathetic Stimulation With Bethanechol in Localized Pancreatic Adenocarcinoma Prior to Surgery
Actual Study Start Date : April 8, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : October 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Bethanechol
Patients with pancreatic adenocarcinoma will receive bethanechol prior to pancreatic surgery
Drug: Bethanechol
Supplied as 50mg oral tablets. Take 2 tablets (total 100mg) twice daily from day 1 for a minimum of 1 week and a maximum of 4 weeks (or 2 days prior to scheduled surgery). Medication should be taken 1 hour before meals in the morning and the evening. Although bethanechol is FDA approved, in this study its use is experimental.
Other Name: Bethanechol chloride tablet




Primary Outcome Measures :
  1. Change in cell proliferation by Ki-67 expression in tumor cells [ Time Frame: Baseline, 28 days after surgery ]
    Individual tumor tissues will be evaluated, comparing pre-treatment and post-treatment samples. Percentage of change in proliferation/staining and standard deviation will be analyzed and calculated.


Secondary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: Baseline, 28 days after surgery ]
    Subjects will be contacted every week (+/- 3 days) after the start of treatment to approximately 28 days after surgery.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be willing and able to provide written informed consent for the trial.
  • Age ≥18 years of age on the day of signing informed consent.
  • Have histologically or cytologically confirmed the diagnosis of resectable pancreatic ductal adenocarcinoma or be willing to undergo a biopsy with confirmed pathology prior to starting therapy.
  • Have a predicted life expectancy of greater than 3 months.
  • Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale within 3 days of the first dose of study drug.
  • Have a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication (Cycle 1, Day 1) (female subjects of childbearing potential). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria:

  • Has received prior chemotherapy or radiotherapy for a current episode of pancreatic adenocarcinoma.
  • Is currently using an acetylcholinesterase inhibitor or a beta-blocker.
  • Has active peptic ulcer disease as defined by documented peptic ulcer and symptoms uncontrolled with oral medication.
  • Has a known hypersensitivity or allergy to bethanechol.
  • Has uncontrolled hyperthyroidism, defined as clinical hyperthyroidism uncontrolled by oral medication.
  • Has bradycardia with resting heart rate < 50 beats per minute.
  • Has chronic hypotension with resting systolic blood pressure < 90 mmHg.
  • Has symptomatic coronary artery disease, such as angina or symptoms of claudication
  • Has vasomotor instability.
  • Has seizure disorder or required anti-seizure medication for seizure prevention within 5 years prior to study entry.
  • Has a history of Parkinson's disease.
  • Has bronchial asthma.
  • Has a history of recent urinary bladder surgery within 12 months of study entry.
  • Has a history of gastrointestinal resection and anastomosis within 12 months of study entry.
  • Has a history of current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03572283


Contacts
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Contact: Lisa Olmos, RN (212) 342-5162 cancerclinicaltrials@cumc.columbia.edu

Locations
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United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Susan Bates, MD       seb2227@cumc.columbia.edu   
Principal Investigator: Susan Bates, MD         
Sponsors and Collaborators
Columbia University
Investigators
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Principal Investigator: Susan E Bates, MD Columbia University
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Responsible Party: Susan E. Bates, Professor of Medicine at Columbia University Medical Ctr, Columbia University
ClinicalTrials.gov Identifier: NCT03572283    
Other Study ID Numbers: AAAR6735
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Susan E. Bates, Columbia University:
Pancreas
pancreatic adenocarcinoma
adenocarcinoma
bethanechol
parasympathetic
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Bethanechol
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action