Chemo + EUS-RFA for Pancreatic Cancer

Overseen By Emil Agarunov

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NYU Langone Health

Disqualifiers: Distant metastasis, Pregnancy, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 15 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm study in the treatment of pancreatic ductal adenocarcinoma (PDAC). The investigators propose to test the tolerability of chemotherapy plus endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) using the RF Electrode in patients receiving palliative second or third line therapy for unresectable non-metastatic pancreatic cancer.

Do I need to stop my current medications for this trial?

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 Chemo + EUS-RFA for Pancreatic Cancer?

Research shows that chemotherapy can slightly improve survival and quality of life in some pancreatic cancer patients, although its overall effectiveness is limited. Combining chemotherapy with surgery has been suggested to improve survival rates, and newer treatments like gemcitabine have shown better results with fewer side effects compared to older drugs. ^{1 2 3 4 5}

Is the combination of chemotherapy and EUS-RFA generally safe for humans?

Chemotherapy for pancreatic cancer can cause moderate-to-severe side effects, and managing these side effects often requires additional medications. EUS-guided procedures, like pancreatic cyst chemoablation, have been found to be safe for selected patients. ^{6 7 8 9 10}

How is the treatment Chemo + EUS-RFA unique for pancreatic cancer?

Chemo + EUS-RFA is unique because it combines chemotherapy with a minimally invasive technique called endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA), which targets and destroys cancer cells directly in the pancreas, potentially reducing side effects compared to traditional surgery. ^{11 12 13 14 15}

Research Team

Tamas A. Gonda, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for individuals with pancreatic cancer that hasn't spread far (locally advanced) and is between 1-4cm in size. They should have tried chemotherapy already without success, be reasonably well (ECOG 0-2), and not be candidates for surgery. Pregnant people or those who can't consent, have tumors smaller than 1cm or larger than 4cm, or masses that can't be reached endoscopically are excluded.

Inclusion Criteria

My cancer lesion is between 1 to 4 cm in size.

My pancreatic cancer diagnosis was confirmed through a biopsy.

I can take care of myself and perform daily activities.

Exclusion Criteria

My cancer has spread to distant parts of my body.

My cancer lesions are either smaller than 1cm or larger than 4cm.

Inability to provide informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy and undergo EUS-RFA procedures

15 weeks

3 EUS-RFA procedures, multiple chemotherapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 weeks

Treatment Details

Interventions

• Chemotherapy
• Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA)

Trial Overview The study tests how well patients handle a combination of chemotherapy and a procedure called Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA). It's given to those whose pancreatic cancer remains after initial chemo but hasn’t metastasized.

Participant Groups

Group I: Chemotherapy plus EUS-RFA Experimental Treatment 2 Interventions

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) and chemotherapy will be administered as part of standard of care treatment for PDAC in patients receiving palliative second- or third-line therapy for unresectable non-metastatic pancreatic cancer. Study participants will undergo 3 identical EUS-RFA procedures, administered during Study Window 2 (Weeks 1-3), Window 3 (Weeks 5-7), and Window 4 (Weeks 9-11). During each EUS-RFA procedure, a tumor biopsy will also be taken for single cell RNA sequencing. Chemotherapy will be administered during Study Window 2 (Weeks 1-3), Window 3 (Weeks 5-7), Window 4 (Weeks 9-11), and Window 5 (Weeks 13-15).

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

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Taewoong Medical

Collaborator

Trials

1

Recruited

20+

Findings from Research

Chemotherapy for advanced pancreatic cancer shows low overall activity but can provide a slight survival benefit and improve quality of life for some patients, as indicated by a systematic review of eight small randomized trials.

While gemcitabine is an approved treatment in some countries, there is no standard chemotherapy regimen established, and conclusive evidence for the use of adjuvant chemotherapy remains lacking due to the small number of patients in relevant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of cancer of the pancreas. Glimelius, B.[2022]

A systematic review of 10 randomized studies involving 4,028 patients found no convincing evidence that adjuvant chemotherapy improves outcomes for pancreatic cancer patients, suggesting it should not be used routinely.

In cases of locally advanced or metastatic pancreatic cancer, some chemotherapy regimens showed a modest survival benefit of 3 to 9 months, but overall, palliative chemotherapy should be used selectively and preferably within clinical trials due to limited effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic overview of chemotherapy effects in pancreatic cancer. Permert, J., Hafström, L., Nygren, P., et al.[2022]

Adding adjuvant chemotherapy to surgery for localized pancreatic adenocarcinoma may improve overall survival rates, as suggested by the ESPAC-1 trial, despite the chemotherapy regimens being considered less effective for advanced disease.

The role of radiotherapy in combination with chemotherapy remains unclear, but it is still being explored as part of a comprehensive treatment strategy for localized pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined-modality treatment for operable pancreatic adenocarcinoma. Pisters, PW., Wolff, RA., Crane, CH., et al.[2007]

Pancreatic cancer has a very poor prognosis, with a 5-year survival rate being rare for most patients due to late diagnosis and aggressive disease spread, highlighting the need for careful evaluation and awareness of treatment options.

While surgical resection can offer long-term survival for localized cancers, the addition of postoperative radiation therapy improves local control but has minimal impact on overall survival, which is primarily affected by the development of liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical recommendations for the management of adenocarcinoma of the pancreas. Sporn, JR.[2018]

Neoadjuvant therapy, specifically gemcitabine-based chemo(radio)therapy, significantly improves overall survival (OS) in patients with borderline resectable pancreatic cancer, increasing median OS from 19 to 29 months compared to upfront surgery.

In patients with resectable pancreatic cancer, there was no significant difference in OS when comparing neoadjuvant therapy to upfront surgery, indicating that more research is needed to determine the benefits of neoadjuvant therapy in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: A meta-analysis of randomised controlled trials. van Dam, JL., Janssen, QP., Besselink, MG., et al.[2022]

In a study of 825 patients with metastatic pancreatic ductal adenocarcinoma receiving second-line chemotherapy, those treated with liposomal irinotecan-based regimens experienced the lowest rates of severe blood-related adverse events like anemia, neutropenia, and thrombocytopenia compared to other regimens such as FOLFIRINOX and FOLFOX.

Patients on liposomal irinotecan also required similar or fewer medications to manage these adverse events, indicating a potentially safer and more manageable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma. Kim, G., Cockrum, P., Surinach, A., et al.[2023]

Concurrent chemotherapy and radiotherapy for pancreatic adenocarcinoma can lead to predictable acute toxicities that vary based on the intensity of the treatment and the specifics of the radiotherapy, highlighting the importance of careful management.

Proactive planning and management of both surgical complications and treatment toxicities are crucial to prevent unplanned treatment interruptions and ensure patients can complete their therapy effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supportive care considerations during concurrent chemoradiotherapy for pancreatic adenocarcinoma: lessons learned from clinical experience. Wang-Gillam, A., Abrams, RA., Posner, MC., et al.[2013]

In a study of 52 patients who underwent endoscopic ultrasound-guided pancreatic cyst chemoablation, 69.2% achieved complete response and all patients could safely reduce their radiographic surveillance to annual or less without recurrence or malignancy.

The ChARM Post-treatment Reduced Radiographic Surveillance Protocol significantly lowered healthcare costs to $7200 compared to $19,437.44 and $12,526.52 under the Fukuoka and ACG guidelines, respectively, while most patients preferred this reduced surveillance approach due to lower logistical and emotional burdens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does successful EUS-guided pancreatic cyst chemoablation safely allow reduction in the frequency of radiographic surveillance? Long-term follow-up of randomized prospective data. Moyer, MT., Heinle, JW., Rhoades, SE., et al.[2023]

In a study of 59 patients with advanced pancreatic cancer receiving outpatient chemotherapy, moderate-to-severe adverse events like anorexia, pain, and peripheral neuropathy were linked to a significant decrease in quality of life (QOL).

Pharmaceutical interventions targeting these specific adverse events were found to improve patients' QOL, suggesting that managing these side effects can enhance the overall treatment experience for patients undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anorexia, pain and peripheral neuropathy are associated with a decrease in quality of life in patients with advanced pancreatic cancer receiving outpatient chemotherapy - a retrospective observational study. Fujii, H., Koda, M., Sadaka, S., et al.[2021]

In a study of 126 patients with borderline resectable pancreatic cancer, those receiving neoadjuvant therapy reported a high incidence of symptomatic adverse events (AEs), with fatigue (36%) and dry mouth (21%) being the most common grade 3 or higher AEs.

Patient-reported outcomes (PRO-CTCAE) revealed that symptomatic AEs were reported more frequently than those recorded by clinicians, highlighting the importance of patient feedback in understanding the full impact of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported Adverse Events During Neoadjuvant Therapy in a Phase 2 Borderline Resectable Pancreatic Cancer Clinical Trial (Alliance A021501). Snyder, RA., Dueck, AC., Fruth, B., et al.[2023]

Patients with unresectable pancreatic ductal adenocarcinoma who received EUS-guided radiofrequency ablation (EUS-RFA) along with systemic chemotherapy showed a significantly higher rate of tumor necrosis (100%) compared to those who received chemotherapy alone (50%).

The EUS-RFA group also experienced a significant reduction in narcotic pain medication usage, decreasing from an average of 63.6 mg to 37.1 mg per day, while the chemotherapy-only group did not see a reduction in pain medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EUS-guided radiofrequency ablation plus chemotherapy versus chemotherapy alone for pancreatic cancer (ERAP): An observational open-label pilot study. Kongkam, P., Tiankanon, K., Seo, DW., et al.[2023]

EUS-guided radiofrequency ablation (EUS-RFA) was found to be feasible and effective in creating a necrotic lesion in the pancreas of 10 adult mini pigs, with an average ablation diameter of 23.0 mm.

The procedure showed a good safety profile, as no major complications occurred and all pigs survived without distress for 7 days post-procedure, indicating potential for further research in human applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EUS-guided radiofrequency ablation of the porcine pancreas. Kim, HJ., Seo, DW., Hassanuddin, A., et al.[2016]

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising minimally invasive treatment for pancreatic neuroendocrine tumors and precancerous cystic lesions, providing an alternative for high-risk patients who cannot undergo traditional surgery.

EUS-RFA may also benefit patients with non-surgical pancreatic adenocarcinoma, potentially improving treatment outcomes through its systemic immunomodulatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review on Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of Pancreatic Lesions. Karaisz, FG., Elkelany, OO., Davies, B., et al.[2023]

Endoscopic ultrasound (EUS) is a less invasive method for delivering antitumor therapies directly to intra-abdominal lesions, particularly in the pancreas, which allows for precise targeting.

Preliminary results suggest that EUS-guided therapy is feasible for treating both solid and cystic pancreatic tumors, but further randomized controlled trials are needed to confirm its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic Ultrasound-Guided Antitumor Therapy. Nakai, Y.[2023]

Endoscopic ultrasound guided radiofrequency ablation (EUS-RFA) is a promising less-invasive alternative to surgical resection for treating pancreatic tumors, offering high clinical success with minimal injury to surrounding tissues.

EUS-RFA has been shown to have acceptable side effects, making it a viable option for patients with unresectable or recurrent pancreatic cancers, thus addressing the need for safer therapeutic interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EUS-RFA of the pancreas: where are we and future directions. Gollapudi, LA., Tyberg, A.[2022]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Chemotherapy in the treatment of cancer of the pancreas. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A systematic overview of chemotherapy effects in pancreatic cancer. [2022]

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

Combined-modality treatment for operable pancreatic adenocarcinoma. [2007]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Practical recommendations for the management of adenocarcinoma of the pancreas. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: A meta-analysis of randomised controlled trials. [2022]

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

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma. [2023]

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

Supportive care considerations during concurrent chemoradiotherapy for pancreatic adenocarcinoma: lessons learned from clinical experience. [2013]

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

Does successful EUS-guided pancreatic cyst chemoablation safely allow reduction in the frequency of radiographic surveillance? Long-term follow-up of randomized prospective data. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Anorexia, pain and peripheral neuropathy are associated with a decrease in quality of life in patients with advanced pancreatic cancer receiving outpatient chemotherapy - a retrospective observational study. [2021]

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

Patient-reported Adverse Events During Neoadjuvant Therapy in a Phase 2 Borderline Resectable Pancreatic Cancer Clinical Trial (Alliance A021501). [2023]

11. China pubmed.ncbi.nlm.nih.gov

EUS-guided radiofrequency ablation plus chemotherapy versus chemotherapy alone for pancreatic cancer (ERAP): An observational open-label pilot study. [2023]

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

EUS-guided radiofrequency ablation of the porcine pancreas. [2016]

13. Switzerland pubmed.ncbi.nlm.nih.gov

A Review on Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of Pancreatic Lesions. [2023]

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

Endoscopic Ultrasound-Guided Antitumor Therapy. [2023]

15. China pubmed.ncbi.nlm.nih.gov

EUS-RFA of the pancreas: where are we and future directions. [2022]