Chemotherapy + Alcohol Ablation for Pancreatic Cysts

(CHARM Trial)

Recruiting at 1 trial location

Overseen By Sydney Rhoades, BS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Milton S. Hershey Medical Center

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

75 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of chemotherapeutic pancreatic cyst ablation using ethanol lavage followed by the infusion of a dual-agent chemotherapeutic cocktail (paclitaxel + gemcitabine) compared with alcohol-free saline lavage followed by infusion of the same dual-agent chemotherapeutic cocktail (paclitaxel + gemcitabine) for the ablation of pancreatic cystic neoplasms using endoscopic ultrasound guided fine needle infusion (EUS-FNI) for agent delivery.

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.

What data supports the effectiveness of the treatment for pancreatic cysts?

Research shows that using a combination of alcohol and paclitaxel for treating pancreatic cysts can lead to complete cyst resolution in about 72% of patients, with most remaining cyst-free for years. However, there are some risks of complications, and the treatment's long-term impact on preventing pancreatic cancer is still unclear. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs nab-paclitaxel and gemcitabine safe for treating pancreatic cancer?

The combination of nab-paclitaxel and gemcitabine has been studied in various trials and is generally considered safe for treating pancreatic cancer, with safety data available from both clinical trials and real-life practice settings. ^{6 7 8 9 10}

How is the chemotherapy and alcohol ablation treatment for pancreatic cysts different from other treatments?

This treatment is unique because it combines chemotherapy drugs, Paclitaxel and Gemcitabine, with alcohol ablation, which is a method that uses alcohol to destroy tissue. This combination aims to enhance the effectiveness of chemotherapy by directly targeting pancreatic cysts, potentially offering a more focused approach compared to traditional systemic chemotherapy. ^{7 8 9 10 11}

Research Team

Matthew T. Moyer, MD, MS

Principal Investigator

Penn State Health Milton S Hershey Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The Safety and Efficacy of an Alcohol-Free Pancreatic Cyst Ablation Protocol. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Endoscopic ultrasound-guided pancreatic cyst ablation. [2012]

3. England pubmed.ncbi.nlm.nih.gov

The efficacy and safety of endoscopic ultrasound-guided ablation of pancreatic cysts with alcohol and paclitaxel: a systematic review. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Long-term outcomes after endoscopic ultrasound-guided ablation of pancreatic cysts. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Alterations in cyst fluid genetics following endoscopic ultrasound-guided pancreatic cyst ablation with ethanol and paclitaxel. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study. [2022]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Combination of gemcitabine, nab-paclitaxel, and S-1(GAS) as the first-line treatment for patients with locally advanced or advanced pancreatic ductal adenocarcinoma: study protocol for an open-label, single-arm phase I study. [2022]

11. England 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. [2022]