Pancreas CancerEarly Phase 1NCT03572283
Bethanechol Prior to Pancreatic Surgery
A Early Phase 1 study testing Bethanechol in people with Pancreas Cancer, run by Columbia University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreas Cancer
- What is being tested?
- Bethanechol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Apr 2018to 24 Aug 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- 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
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Phase 1 Window of Opportunity Study of Parasympathetic Stimulation With Bethanechol in Localized Pancreatic Adenocarcinoma Prior to Surgery
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.
Read the 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.
.
- Conditions
- Pancreas Cancer
- Being tested
- Bethanechol
- Keywords
- Pancreas, pancreatic adenocarcinoma, adenocarcinoma, bethanechol, parasympathetic
- Medical subject headings
- Pancreatic Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BethanecholDrug
Also called Bethanechol chloride tablet
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.
| Study group | Role | What they receive |
|---|---|---|
| Bethanechol | Experimental | Patients with pancreatic adenocarcinoma will receive bethanechol prior to pancreatic surgery Receives: Drug: Bethanechol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cell proliferation by Ki-67 expression in tumor cells
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.
Measured: Baseline, 28 days after surgery
Secondary outcomes (1)
Number of Adverse Events
Subjects will be contacted every week (+/- 3 days) after the start of treatment to approximately 28 days after surgery.
Measured: Baseline, 28 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2018
- Study start8 Apr 2018
- Primary completion25 Jul 2023
- Study completion24 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreas CancerStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase 0 study to assess the impact of bethanechol on pancreatic cancer biomarkers
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Susan E. Bates, Columbia University
- Investigators
- Susan E Bates, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03572283
- Sponsor's protocol ID
- AAAR6735
- Status last verified
- May 2025
- First submitted
- 8 May 2018
- Last updated
- 5 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Window of Opportunity Study of Parasympathetic Stimulation With Bethanechol in Localized Pancreatic Adenocarcinoma Prior to Surgery
- ClinicalTrials.gov ID
- NCT03572283
- Acronym / sponsor ID
- AAAR6735
- Conditions
- Pancreas Cancer
- Keywords
- Pancreas, pancreatic adenocarcinoma, adenocarcinoma, bethanechol, parasympathetic
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 8 Apr 2018 (actual)
- Primary completion
- 25 Jul 2023 (actual)
- Study completion
- 24 Aug 2023 (actual)
- First posted
- 28 Jun 2018 (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.
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.
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.
.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 0 study to assess the impact of bethanechol on pancreatic cancer biomarkers
| Arm | Type | Receives |
|---|---|---|
| Bethanechol | Experimental | Drug: BethanecholPatients with pancreatic adenocarcinoma will receive bethanechol prior to pancreatic surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
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 |
|---|---|---|
| BethanecholAlso: Bethanechol chloride tabletSupplied 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. | Drug | Bethanechol |
Primary outcome
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.
1 secondary outcome
Number of Adverse Events
Time frame: Baseline, 28 days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
- 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. This study is not recruiting at the moment.
Susan E Bates, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Bethanechol in people with Pancreas Cancer, run by Columbia University at 1 site in United States.
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 6 inclusion and 17 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: finished, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cell proliferation by Ki-67 expression in tumor cells (time frame: Baseline, 28 days after surgery). 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 5 Jun 2025.