Chemotherapy + Alcohol Ablation for Pancreatic Cysts

(CHARM Trial)

Not currently recruiting at 1 trial location

Overseen By Sydney Rhoades, BS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Milton S. Hershey Medical Center

Disqualifiers: Pancreatic cancer, Acute pancreatitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating pancreatic cysts, which are fluid-filled sacs that can form in the pancreas. Researchers compare two approaches: one involves rinsing with alcohol (ethanol) before delivering chemotherapy drugs, and the other uses a saline (saltwater) rinse before the same chemotherapy treatment. The goal is to determine which method is more effective and safer for shrinking or eliminating these cysts. Suitable candidates for this trial are those with pancreatic cysts measuring 2-5 cm wide that are not clearly non-cancerous. Participants must be able to safely undergo a procedure using a camera and needle to deliver the treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that using a combination of paclitaxel and gemcitabine to treat pancreatic cysts is generally safe. In studies using this combination, most patients did not experience serious side effects. Some reported mild to moderate issues, such as nausea or fatigue, but these were uncommon. Paclitaxel and gemcitabine are already FDA-approved for other uses, indicating a known safety record. Doctors have safely used these drugs in other treatments. Overall, evidence suggests that the treatment is safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for pancreatic cysts, which often involve surgical removal or surveillance, this new approach combines chemotherapy with a novel delivery method. Researchers are excited about using an admixture of paclitaxel and gemcitabine, which are infused directly into the cyst after lavage. This targeted delivery system could potentially enhance the effectiveness of the drugs by concentrating them where they're needed most, possibly reducing systemic side effects. Additionally, by experimenting with ethanol versus saline lavage, the trial seeks to determine the optimal preparation technique for enhancing drug absorption.

What evidence suggests that this trial's treatments could be effective for pancreatic cysts?

Research has shown that using the drugs paclitaxel and gemcitabine to treat pancreatic cysts is effective. In one study, 87% of patients who fully responded to this treatment had their cysts resolved for the long term. Another study found that 50% of patients had their cysts completely removed or destroyed after one year, and 61.7% maintained this result after two years. In this trial, participants in both the control and study groups will receive an admixture of paclitaxel and gemcitabine directly into the cyst, effectively targeting the problem area. The control group will have their cysts lavaged with ethanol before the admixture, while the study group will use normal saline for lavage. These two drugs work well together, enhancing each other's ability to fight the tumor, and this treatment is considered safe. ^{2 3 6 7 8}

Who Is on the Research Team?

Matthew T. Moyer, MD, MS

Principal Investigator

Penn State Health Milton S Hershey Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with a pancreatic cyst 2-5 cm in size, likely mucinous based on ASGE guidelines. Participants must be able to undergo endoscopy with sedation or anesthesia and provide consent. Excluded are those with benign cysts, suspected cancer, certain high-risk cyst features, recent pancreatitis, abnormal lab values (like blood cell counts and liver enzymes), severe medical conditions affecting life expectancy under five years, pregnant or breastfeeding women.

Inclusion Criteria

I am over 18 years old.

I can safely undergo procedures with deep sleep or general anesthesia.

I have a pancreatic cyst between 2-5 cm, likely mucinous.

Exclusion Criteria

My pancreatic cyst has features that may suggest a higher risk of cancer.

Baseline lab values (must be within 6 months of consent date) outside specified ranges

I was diagnosed with acute pancreatitis in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo EUS-FNI procedure with either ethanol or saline lavage followed by infusion of paclitaxel and gemcitabine

1 day

1 visit (in-person)

Initial Follow-up

Participants are contacted by phone at 72 hours and 30 days post-procedure to assess adverse events

1 month

2 contacts (phone)

3-Month Follow-up

Participants undergo a follow-up EUS examination to assess cyst response and possible repeat ablation

3 months

1 visit (in-person)

Long-term Follow-up

Participants undergo MRI-MRCP or CT scan at 12 and 24 months to assess treatment response

24 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ethanol
• Normal saline
• Paclitaxel + Gemcitabine admixture

Trial Overview The trial is testing the effectiveness of using ethanol lavage followed by paclitaxel + gemcitabine infusion versus saline lavage plus the same chemotherapy cocktail for treating pancreatic cystic neoplasms. The treatments are delivered through an endoscopic ultrasound-guided needle.

How Is the Trial Designed?

Group I: Study group Experimental Treatment 2 Interventions

Cyst will be lavaged for 3 to 5 minutes with normal saline. Following lavage with normal saline, the cyst will be infused with an admixture of (3mg/ml paclitaxel + 19mg/ml gemcitabine).

Group II: Control Group Active Control 2 Interventions

Cyst will be lavaged for 3 to 5 minutes with \>/=99% ethanol. Following lavage with \>/=99% ethanol, the cyst will be infused with an admixture of (3mg/ml paclitaxel + 19mg/ml gemcitabine).

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nabpaclitaxel plus S-1 (AS) significantly improved median time to progression (7.1 months) and overall survival (10.2 months) compared to gemcitabine plus S-1 (GS), indicating AS may be a more effective first-line treatment for metastatic pancreatic cancer based on a study of 38 patients.

While both treatments had similar rates of hematological adverse events, AS was associated with a higher risk of sensory neuropathy, suggesting that while AS is effective, it requires careful monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety comparison of nabpaclitaxel plus S-1 and gemcitabine plus S-1 as first-line chemotherapy for metastatic pancreatic cancer. Xu, Y., Guo, X., Fan, Y., et al.[2022]

Targeted intra-arterial (IA) delivery of gemcitabine directly into the pancreas significantly reduces tumor growth in a mouse model of pancreatic cancer compared to low-dose systemic intravenous (IV) delivery.

To achieve similar tumor reduction effects as IA delivery, a much higher IV dose (over 300 times) is required, which can lead to increased toxicity, highlighting the efficacy and safety benefits of the IA approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Study Comparing the Effects of Targeted Intra-Arterial and Systemic Chemotherapy in an Orthotopic Mouse Model of Pancreatic Cancer. Rezaee, M., Wang, J., Razavi, M., et al.[2022]

In a study involving 866 patients with resected pancreatic ductal adenocarcinoma, the combination of nab-paclitaxel and gemcitabine showed a significant improvement in overall survival (OS) compared to gemcitabine alone, with a median OS of 41.8 months versus 37.7 months, respectively.

Although the primary endpoint of disease-free survival (DFS) was not significantly improved with nab-paclitaxel + gemcitabine, the treatment was associated with a higher incidence of grade ≥ 3 adverse events (86% vs. 68% for gemcitabine), indicating a need for careful consideration of safety alongside efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. Tempero, MA., Pelzer, U., O'Reilly, EM., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8530455/

The Durability of EUS-Guided Chemoablation of Mucinous ... In this report, we show that complete cyst resolution after EUS-guided chemoablation with paclitaxel and gemcitabine is durable, with 87% of complete responders ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6715424/

Position statement on EUS-guided ablation of pancreatic ... Paclitaxel in doses used for pancreatic cyst ablation has been shown to be safe when injected into pancreatic cysts without identifiable blood levels of the ...

3. gastrojournal.org gastrojournal.org/article/S0016-5085(17)36020-1/pdf

The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst ... Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after ...

4. giejournal.org giejournal.org/article/S0016-5107(23)03152-8/fulltext

Successful EUS-guided pancreatic cyst chemoablation ... At 1 year, 26 (50.0%) of all 52 patients achieved complete ablation and 29 of 47 patients (61.7%) were in complete response at 2-year follow-up.

5. aacrjournals.org aacrjournals.org/cancerdiscovery/article/2/3/260/37316/nab-Paclitaxel-Potentiates-Gemcitabine-Activity-by

nab-Paclitaxel Potentiates Gemcitabine Activity by Reducing ... Combined nab-paclitaxel and gemcitabine therapy leads to synergistic antitumor effects due to decreased gemcitabine metabolism.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28802565/

The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst ... Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0016508517360201

The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst ... Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after ...

8. gastrojournal.org gastrojournal.org/article/S0016-5085(17)36020-1/abstract

The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst ... Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after ...