Bethanechol + Chemotherapy for Pancreatic Cancer

Overseen By Susan E Bates, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Susan E. Bates

Must not be taking: Acetylcholinesterase inhibitors

Disqualifiers: Metastatic disease, GI obstruction, bradycardia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding bethanechol to standard chemotherapy can enhance the success of pancreatic cancer surgery by aiding in the removal of all visible tumors. It also evaluates the safety of this combination and its impact on the cancer's growth rate. The trial targets individuals with pancreatic ductal adenocarcinoma who plan to begin chemotherapy before surgery and can take oral medications. Participants should not have metastatic cancer or conditions such as severe heart issues or seizures that might interfere with the treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using acetylcholinesterase inhibitors. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that bethanechol is safe and well-tolerated in patients with pancreatic cancer. Research indicates that this treatment did not cause severe side effects. It has been used to try to slow cancer growth based on animal studies. Although some studies did not achieve their main goals, they confirmed the treatment's safety.

This trial also includes gemcitabine and nab-paclitaxel, standard chemotherapy drugs. These drugs are commonly used, and their safety is well-known. Most patients handle them well, though, like any chemotherapy, they can cause side effects such as tiredness and nausea. Prospective participants should note that past studies and current use suggest these treatments are generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Bethanechol is unique because it targets the nervous system to stimulate the pancreas in a way that existing treatments like chemotherapy alone do not. Most treatments for pancreatic cancer, such as gemcitabine and nab-paclitaxel, directly target cancer cells to stop their growth. However, bethanechol works differently by potentially enhancing the effects of chemotherapy, offering a new angle of attack against the cancer. Researchers are excited about this because it could improve surgical outcomes and make tumors more manageable for removal, potentially leading to better survival rates.

What evidence suggests that bethanechol combined with chemotherapy could be effective for pancreatic cancer?

Research shows that bethanechol, which participants in this trial may receive, might help treat pancreatic cancer when combined with chemotherapy. Animal studies suggest that bethanechol can slow cancer growth and spread. In an earlier study, 69% of patients who took bethanechol had their tumors successfully removed. Additionally, bethanechol treatment decreased certain inflammation markers, potentially reducing tumor activity. These findings offer promising early evidence that bethanechol could be effective when combined with chemotherapy for pancreatic cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Susan E Bates, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for individuals with Pancreatic Ductal Adenocarcinoma who are planning to undergo neoadjuvant chemotherapy. They must have tissue available for biomarker analysis and be able to take oral medications. People with metastatic disease, GI obstruction, very low heart rate or blood pressure, or certain medical conditions like hyperthyroidism cannot participate.

Inclusion Criteria

I am scheduled for chemotherapy before surgery.

I can take pills and follow study rules.

I have been diagnosed with pancreatic cancer.

Exclusion Criteria

I have a blockage in my digestive tract.

You have a slow heart rate (less than 55 beats per minute) or low blood pressure (less than 90 for the top number).

I do not have hyperthyroidism, active heart disease, seizures, or stomach ulcers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bethanechol in combination with gemcitabine and nab-paclitaxel for a minimum of 2 months

8 weeks

Surgery

Participants undergo surgery after treatment with bethanechol and chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Bethanechol
• Gemcitabine
• Nab-paclitaxel

Trial Overview The study tests the effect of bethanechol combined with gemcitabine and nab-paclitaxel on pancreatic cancer surgery success rates (R0 resection). It also looks at safety and explores how this treatment might affect tumor growth and genomic markers related to parasympathetic stimulation.

How Is the Trial Designed?

Group I: Bethanechol Experimental Treatment 3 Interventions

Patients with borderline resectable pancreatic cancer and no contraindication to bethanechol therapy will receive bethanechol on day 1 and continue until 2 days prior to scheduled surgery for a minimum of 2 months.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Susan E. Bates

Lead Sponsor

Trials

2

Recruited

70+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40448309/

A phase 0, window of opportunity study of parasympathetic ... Bethanechol treatment was associated with decreased Granzyme B positive cells and decreased circulating IL-18 consistent with an anti- ...

2. academic.oup.com academic.oup.com/oncolo/advance-article/doi/10.1093/oncolo/oyaf162/8154263?searchresult=1

A phase 0, window of opportunity study of parasympathetic ... Pancreatic adenocarcinoma (PDAC) is a highly aggressive malignancy with a five-year overall survival rate of approximately 10%.4 Progress in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03572283?term=BETHANECHOL&viewType=Table&rank=2

NCT03572283 | Bethanechol Prior to Pancreatic 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05241249

Stimulation With Bethanechol in Combination ... Animal models have shown that treatment with bethanechol can inhibit cancer growth and spread. The chemotherapy regimen nab-paclitaxel for use in combination ...

5. researchgate.net researchgate.net/publication/392270311_A_Phase_0_Window_of_Opportunity_Study_of_Parasympathetic_Stimulation_with_Bethanechol_in_Localized_Pancreatic_Adenocarcinoma_Prior_to_Surgery

(PDF) A Phase 0, Window of Opportunity Study ... R0 resections were achieved in 9 patients (69%). There was no difference in Ki67 and CD44 tissue biomarkers between bethanechol-treated and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12203072/

A phase 0, window of opportunity study of parasympathetic ... Bethanechol treatment was associated with decreased Granzyme B positive cells and decreased circulating IL-18 consistent with an anti- ...

7. npcf.us npcf.us/clinical-trials/bethanechol-prior-to-pancreatic-surgery/

Bethanechol Prior To Pancreatic Surgery The investigators planned this study in pancreatic cancer because animal models have shown that treatment with bethanechol can inhibit cancer growth and spread.

8. academic.oup.com academic.oup.com/oncolo/article-pdf/30/6/oyaf162/63409492/oyaf162.pdf

oyaf162.pdf - Oxford Academic 13 Together, these data demonstrate the safety and tolerability of bethanechol in. PDAC patients. The study did not meet the primary endpoint of ...