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

Trial Summary

What is the purpose of this trial?

The objectives of this study are to determine the feasibility, tolerability, and treatment effect of endoscopic ultrasound (EUS) radiofrequency ablation (RFA) plus standard-of-care neoadjuvant chemotherapy (NAC) in the treatment of pancreatic ductal adenocarcinoma (PDAC). Endoscopic ultrasound (EUS) radiofrequency ablation (RFA) and neoadjuvant chemotherapy (NAC) will be performed before tumor resection surgery, with the goal of shrinking a tumor or stopping the spread of cancer so that surgery might be less invasive and more effective.

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 EUS-Guided RFA + Chemotherapy for Pancreatic Cancer?

Research shows that neoadjuvant chemotherapy (NAC) can help shrink tumors in pancreatic cancer, making surgery more successful. This suggests that combining NAC with other treatments like EUS-Guided RFA might improve outcomes for patients. ^{1 2 3 4 5}

Is EUS-Guided RFA + Chemotherapy safe for humans?

The research articles primarily discuss the safety of neoadjuvant chemotherapy (NAC) for pancreatic cancer, indicating that it is generally well tolerated with some manageable side effects like low white blood cell count and low platelet count. However, there is no specific safety data available for EUS-Guided Radiofrequency Ablation (RFA) combined with chemotherapy in these studies. ^{1 3 4 6 7}

How is the treatment EUS-Guided RFA + Chemotherapy for Pancreatic Cancer different from other treatments?

This treatment combines EUS-guided RFA (a technique using heat to destroy cancer cells) with neoadjuvant chemotherapy (NAC), which is given before surgery to shrink tumors and improve surgical outcomes. This combination is unique because it integrates a local treatment (RFA) with systemic chemotherapy, potentially enhancing the effectiveness of preoperative cancer management. ^{1 2 3 5 8}

Research Team

Nirav Thosani, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy Enhances Local Postoperative Histopathological Tumour Stage in Borderline Resectable Pancreatic Cancer - A Matched-Pair Analysis. [2023]

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

No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer. [2023]

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

Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effect and limitation of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma: consideration from a new perspective. [2021]

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

Neoadjuvant chemotherapy for primary resectable pancreatic cancer: a systematic review and meta-analysis. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Impact of adverse events of adjuvant and neoadjuvant chemotherapies on outcomes of patients with pancreatic ductal adenocarcinoma. [2023]

7. Greece pubmed.ncbi.nlm.nih.gov

Pilot study of neoadjuvant chemotherapy with gemcitabine and oral S-1 for resectable pancreatic cancer. [2022]

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

Clinical Efficacy of Neoadjuvant Chemotherapy with Gemcitabine plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma Compared with Upfront Surgery. [2023]