EUS-Guided RFA + Chemotherapy for Pancreatic Cancer

(PANCARDINAL-1 Trial)

Overseen By Sofia C Colon, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Under 18, Pregnant, Inmates, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for pancreatic cancer. It combines endoscopic ultrasound radiofrequency ablation, which uses heat to target and destroy cancer cells, with standard chemotherapy. The aim is to determine if this approach can shrink the tumor or prevent the cancer from spreading before surgery, making the surgery less invasive and more effective. Individuals diagnosed with pancreatic cancer, confirmed by a biopsy, and who have not undergone extensive prior chemotherapy might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in pancreatic cancer 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.

What prior data suggests that endoscopic ultrasound-guided radiofrequency ablation plus neoadjuvant chemotherapy is safe for treating pancreatic cancer?

Research has shown that endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is generally well-tolerated by patients with advanced pancreatic cancer. One study found that EUS-RFA is safe, with most patients experiencing only mild side effects, and serious complications were rare.

For neoadjuvant chemotherapy (NAC), studies indicate it is safe for people with pancreatic cancer, including those whose tumors can be removed by surgery or are borderline operable. Reports often highlight its benefits in improving outcomes and survival, with side effects usually being manageable.

Both treatments have undergone careful study, showing promising safety results. However, discussing any concerns with a healthcare professional is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of neoadjuvant chemotherapy (NAC) with endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for pancreatic cancer because it offers a unique approach to treating this tough-to-tackle disease. While standard treatments usually involve surgery, chemotherapy, and in some cases, radiation, this method introduces a novel technique where EUS-RFA targets and destroys cancer cells directly within the pancreas. This localized treatment could enhance the effectiveness of chemotherapy by shrinking the tumor before surgery, potentially leading to better outcomes. By combining these methods, there's hope for increased precision in attacking cancer cells while sparing more of the healthy surrounding tissue.

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

Research has shown that endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) might offer promise for advanced pancreatic cancer. Studies have found EUS-RFA to be generally safe and as effective as surgery. In this trial, participants will receive a combination of EUS-RFA and neoadjuvant chemotherapy (NAC). NAC plays a crucial role in extending patient survival by shrinking tumors and reducing the risk of residual cancer cells post-surgery. Combining these treatments may enhance disease control and increase surgical success. ^{1 4 6 7 8}

Who Is on the Research Team?

Nirav Thosani, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults with pancreatic cancer confirmed by biopsy, who are in fair to good physical condition (ECOG 0-2), and have either not had chemotherapy or less than two months of it. They must have a permanent address and agree to participate. It's not open to prisoners, those without a phone number, anyone unable to consent, or pregnant individuals.

Inclusion Criteria

Axial CT scan consistent with PDAC

Permanent street address and consent to study participation

I have not had chemotherapy, or had less than 2 months of it for pancreatic cancer.

Exclusion Criteria

I am unable to understand and give consent for treatment.

Inmates or prisoners

I am over 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy and EUS-RFA

Participants receive neoadjuvant chemotherapy and endoscopic ultrasound-guided radiofrequency ablation to shrink the tumor or stop the spread of cancer before surgery

8 weeks

Surgery

Tumor resection surgery is performed after neoadjuvant treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including radiographic treatment response assessment using RECIST criteria

2 months

Long-term Follow-up

Participants are monitored for disease-free survival time, up to 5 years after diagnosis

What Are the Treatments Tested in This Trial?

Interventions

• Endoscopic Ultrasound (EUS)-Guided Radiofrequency Ablation (RFA)
• Endoscopic Ultrasound (EUS) Radiofrequency Ablation (RFA)
• Neoadjuvant chemotherapy (NAC)

Trial Overview The study tests the combination of Endoscopic Ultrasound-guided Radiofrequency Ablation (EUS-RFA) with standard Neoadjuvant chemotherapy (NAC). The goal is to shrink the tumor before surgery, potentially making the operation less invasive and more successful.

How Is the Trial Designed?

Group I: Neoadjuvant chemotherapy (NAC) plus endoscopic ultrasound (EUS) radiofrequency ablation (RFA) Experimental Treatment 2 Interventions

Neoadjuvant chemotherapy (NAC) is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Neoadjuvant chemotherapy for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Lung cancer

Approved in United States as Neoadjuvant chemotherapy for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Lung cancer

Approved in Canada as Neoadjuvant chemotherapy for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Lung cancer

Approved in Japan as Neoadjuvant chemotherapy for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Lung cancer

Approved in China as Neoadjuvant chemotherapy for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Lung cancer

Approved in Switzerland as Neoadjuvant chemotherapy for:

• Breast cancer
• Ovarian cancer
• Colorectal cancer
• Pancreatic cancer
• Lung cancer

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 131 pancreatic ductal adenocarcinoma (PDAC) patients, those who received neoadjuvant chemotherapy (NAC) showed smaller tumor sizes and lower rates of nodal and distant metastasis compared to those who underwent upfront surgery (UFS).

Despite these findings, the overall and disease-free survival rates were similar between the NAC and UFS groups, indicating that while NAC may help in downstaging tumors, it does not significantly improve postoperative prognosis for most PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and limitation of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma: consideration from a new perspective. Kurata, Y., Shiraki, T., Ichinose, M., et al.[2021]

In patients with pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant chemotherapy (NAC) followed by adjuvant chemotherapy (AC), experiencing severe adverse events (grade 3/4) during AC was linked to significantly worse overall survival and lower treatment completion rates.

The study identified key predictors for severe adverse events during AC, including the type of chemotherapy agent used (gemcitabine), low albumin levels, and reduced kidney function, highlighting the importance of monitoring these factors in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of adverse events of adjuvant and neoadjuvant chemotherapies on outcomes of patients with pancreatic ductal adenocarcinoma. Mori, S., Aoki, T., Sakuraoka, Y., et al.[2023]

Neoadjuvant chemotherapy (NAC) with gemcitabine and oral S-1 in 34 patients with potentially resectable pancreatic cancer showed promising results, with no patients unable to undergo surgery due to disease progression, and stable disease observed in all NAC patients.

The one- and three-year overall survival rates for the NAC group were 88.9% and 55.6%, respectively, which were higher than the control group's rates of 88.9% and 29.6%, suggesting that NAC may improve survival outcomes in patients undergoing surgery for pancreatic head cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of neoadjuvant chemotherapy with gemcitabine and oral S-1 for resectable pancreatic cancer. Tajima, H., Ohta, T., Kitagawa, H., et al.[2022]

Neoadjuvant chemotherapy (NAC) in resectable pancreatic cancer (RPC) is linked to a higher R0 resection rate and a lower rate of positive lymph nodes, suggesting it may improve surgical outcomes despite a lower overall surgical resection rate.

While overall survival rates were similar between patients receiving NAC and those undergoing upfront resection, patients treated with gemcitabine-based NAC showed a potential survival benefit, indicating that specific chemotherapy regimens may enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy for primary resectable pancreatic cancer: a systematic review and meta-analysis. Ye, M., Zhang, Q., Chen, Y., et al.[2021]

In a study of 586 patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC), neoadjuvant chemotherapy (NAC) showed a significant overall survival (OS) benefit when measured from diagnosis, particularly for those achieving an optimal CA19-9 response, which was defined as normalization and over 50% reduction in levels.

Patients with an optimal CA19-9 response had a notably longer OS (39.3 months) compared to those with suboptimal responses (21.5 months) and those who underwent surgery-first (SF) (19.5 months), suggesting that CA19-9 response could be a key marker for the effectiveness of NAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer. Liu, H., D'Alesio, M., AlMasri, S., et al.[2023]

In a study of 468 patients with borderline resectable or locally advanced pancreatic cancer, switching chemotherapy regimens after initial treatment allowed 72% of those patients to undergo curative surgery, demonstrating its potential benefit in treatment planning.

Overall survival and recurrence-free survival rates were similar between patients who continued with the first-line chemotherapy and those who switched, indicating that changing chemotherapy regimens does not negatively impact oncologic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer. Alva-Ruiz, R., Yohanathan, L., Yonkus, JA., et al.[2022]

In a study of 340 patients with resectable pancreatic ductal adenocarcinoma (PDAC), neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) resulted in a significantly higher R0 resection rate (91.3%) compared to upfront surgery (UPS) (82.6%), indicating better surgical outcomes.

Patients receiving NAC-GS also experienced significantly improved overall survival (hazard ratio 0.55) compared to those who underwent upfront surgery, suggesting that NAC-GS may enhance prognosis in resectable PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy of Neoadjuvant Chemotherapy with Gemcitabine plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma Compared with Upfront Surgery. Kitano, Y., Inoue, Y., Takeda, T., et al.[2023]

Neoadjuvant chemotherapy (NAC) significantly reduces lymphatic tissue invasion in patients with borderline-resectable pancreatic cancer, with lower rates of lymph node invasion (51.5% vs. 72.7%) and lymphatic vessel invasion (9.4% vs. 55.3%) compared to those undergoing upfront surgery.

NAC is a safe treatment option, showing no increase in perioperative complications, hospital stay, or mortality, and it even resulted in a lower occurrence of postoperative pancreatic fistula (18.2% vs. 24.3%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy Enhances Local Postoperative Histopathological Tumour Stage in Borderline Resectable Pancreatic Cancer - A Matched-Pair Analysis. Timmermann, L., Rosumeck, N., Klein, F., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11854302/

Endoscopic Ultrasound-Guided Radiofrequency Ablation for ... Despite advances in surgical techniques and chemotherapy, the five-year survival rate for pancreatic cancer barely exceeds 10% [1]. The majority of patients are ...

2. nature.com nature.com/articles/s41598-022-20316-2

Endoscopic ultrasound-guided radiofrequency ablation ... The aim of this study is to report safety-profile, feasibility and outcomes of EUS-RFA for advanced PDAC.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.e16261

Clinical outcomes and efficacy of endoscopic ultrasound ... Common AEs were abdominal pain 7.8% (15), pancreatitis 5.2% (10) and pancreatic pseudocyst 2.1% (4). The median follow-up was 9.5 months.

4. asco.org asco.org/abstracts-presentations/ABSTRACT362694

Efficacy and the safety of endoscopic ultrasound guided ... The pooled AEs rate was 24.6% [95% CI = 0.17-0.39, I2 = 30%]. Common AEs were abdominal pain 10.5% (12), and pancreatitis 3.5% (4). Conclusions: EUS-RFA is a ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1542356523001659

Endoscopic Ultrasound-guided Radiofrequency Ablation ... We found EUS-RFA to be associated with significantly lower overall and severe AE rates, but comparable efficacy to surgery. EUS-RFA was initially used to treat ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36192558/

Endoscopic ultrasound-guided radiofrequency ablation ... The aim of this study is to report safety-profile, feasibility and outcomes of EUS-RFA for advanced PDAC. Prospective review of patients with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03435770

Evaluation of Safety and Feasibility of EUS-guided RFA ... This study aims to evaluate the safety and efficacy of new ablation catheter developed by MEDICAL TAEWOONG for the treatment of pancreatic neoplasm ...

8. reporter.nih.gov reporter.nih.gov/search/8w0Ftp_WB0mrGkGSaRNDYQ/project-details/10846817

Project Details Endoscopic ultrasound guided radiofrequency ablation (EUS-RFA) is a promising local ablative, stromal and immunomodulator therapy for PDAC. We have established ...