Radiofrequency Ablation + Pembrolizumab for Pancreatic Cancer

(PANCARDINAL-2 Trial)

Overseen By Ayodeji Adeniji

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Immunosuppressants, CYP3A inhibitors

Disqualifiers: Pregnancy, CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for pancreatic cancer that cannot be surgically removed. It combines radiofrequency ablation, which destroys cancer cells with heat, with chemotherapy and the immunotherapy drug pembrolizumab. The study aims to determine the safety and effectiveness of this approach for patients with this type of advanced cancer. Ideal participants are those with locally advanced or metastatic pancreatic cancer confirmed through a biopsy, who have not received certain prior treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use strong inhibitors or inducers of certain enzymes (CYP3A, CYP2C8, and UGT1A1) or immunosuppressive medications within 14 days before starting pembrolizumab, except for some specific cases like low-dose steroids.

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

Research has shown that endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is generally safe for treating pancreatic cancer. In one study, about 24.6% of patients experienced side effects. The most common was abdominal pain, affecting 10.5% of patients, while 3.5% experienced pancreatitis, an inflammation of the pancreas. Overall, EUS-RFA is considered safe and technically feasible.

Pembrolizumab, a type of immunotherapy, also has a manageable safety profile for pancreatic cancer patients. Research indicates it can double the one-year survival rate compared to not using it, with a 37% reduction in the risk of death, suggesting it is generally well-tolerated.

Both treatments have demonstrated safety in previous studies, but individual experiences can vary. It is important to consult a healthcare provider to understand the best options. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of radiofrequency ablation (RFA) and pembrolizumab for pancreatic cancer because it introduces a novel approach to treatment. Unlike traditional chemotherapy and surgery, this combination therapy employs RFA to directly target and destroy cancer cells with heat, potentially enhancing the effectiveness of the immune system. Pembrolizumab, an immunotherapy drug, works by unleashing the power of the body's immune system to fight cancer more effectively. This dual approach not only aims to reduce the tumor size before surgery (neoadjuvant chemotherapy) but also potentially increases the chances of a successful long-term outcome by harnessing the body's natural defenses.

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

This trial will evaluate the combination of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) with pembrolizumab and standard chemotherapy for pancreatic cancer. Studies have shown that EUS-RFA effectively reduces pancreatic tumors, with about 91% of treated tumors shrinking. EUS-RFA is considered safe and practical when combined with chemotherapy. Pembrolizumab, a type of immunotherapy, has shown mixed results for pancreatic cancer. In some cases, it has helped shrink tumors in 82% of patients. However, when used alone, pembrolizumab generally benefits less than 5% of pancreatic cancer patients. This trial will explore whether combining these treatments might improve outcomes for people with pancreatic cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Putao Cen

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for individuals with advanced pancreatic cancer that can't be removed by surgery. Participants should have no prior treatments for metastatic disease, and must be able to undergo procedures like endoscopic ultrasound.

Inclusion Criteria

I finished my previous cancer treatment over 6 months ago.

ANC ≥1 x 10^9/L

My pancreatic cancer cannot be removed by surgery and has spread.

Exclusion Criteria

My pancreatic cancer can possibly be removed with surgery.

I am unable to understand and agree to the study's details on my own.

Pregnant or breastfeeding patients or those not employing effective birth control

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EUS-RFA, chemotherapy, and systemic immunotherapy (pembrolizumab) for the treatment of locally advanced unresectable and metastatic pancreatic ductal adenocarcinoma

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Endoscopic Ultrasound Radiofrequency Ablation
• Neoadjuvant Chemotherapy (NAC)
• Pembrolizumab

Trial Overview The study tests a combination of therapies: first, using an endoscope to apply heat (radiofrequency ablation) directly to the tumor; then chemotherapy; followed by pembrolizumab, an immunotherapy drug.

How Is the Trial Designed?

Group I: Standard of care chemotherapy + immunotherapy + EUS-RFA Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study of 41 pancreas cancer patients treated with pembrolizumab, the median overall survival was 7.2 months, which is considered favorable compared to the benchmark of over 4 months.

Patients with specific genetic markers (dMMR, MSI-H, TMB-H, or Lynch syndrome) had a significantly lower risk of death, indicating that these biomarkers may help identify patients who could benefit more from pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. Storandt, MH., Tran, N., Martin, N., et al.[2023]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

Pembrolizumab, a monoclonal antibody used for cancer treatment, can cause rare but severe immune-related toxicities, including myocarditis, as demonstrated in a case of an 83-year-old male who developed fatal myocarditis after two doses.

The COVID-19 pandemic complicated the management of these toxicities, as patients and families were hesitant to seek medical care, highlighting the importance of educating patients about potential symptoms and the need for timely reporting to ensure safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-checkpoint inhibitor toxicity during a pandemic: Overcoming patient fears to provide care. A case report. Elder, CT., Davis, EC., Jaipal, S., 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]

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 phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

In a study involving patients with recurrent platinum-resistant ovarian cancer, the combination of pembrolizumab, cisplatin, and gemcitabine resulted in an overall response rate of 60%, but the duration of response was relatively short at 4.9 months.

The addition of pembrolizumab did not show a significant benefit over chemotherapy alone, leading to the decision to close the trial for further accrual after an interim analysis indicated modest outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. Walsh, CS., Kamrava, M., Rogatko, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11779739/

Efficacy and safety of endoscopic ultrasonography‐guided ... The 6‐month overall survival rate was 100%. Conclusion. EUS‐guided radiofrequency ablation demonstrated a high complete response rate with no ...

2. journals.lww.com journals.lww.com/eusjournal/fulltext/2022/11010/clinical_outcomes_of_eus_guided_radiofrequency.9.aspx

Clinical outcomes of EUS-guided radiofrequency ablation ... Conclusions: EUS-RFA is technically feasible and safe for the management of unresectable pancreatic cancer. EUS-RFA combined with systemic chemotherapy may be ...

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

Clinical outcomes and efficacy of endoscopic ultrasound ... The pooled clinical success rate calculated out of total number of pancreatic lesions was 91.1% [95% CI = 0.79-0.92, I2 = 16%]. Clinical improvement in symptoms ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05916846

Study Details | NCT05916846 | Evaluation of Endoscopic ... This clinical trial evaluates the safety and effectiveness of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for the management of patients ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1521691825000137

Reducing the incidence of pancreatic cancer through ... EUS-RFA is deemed to be safer and highly effective when compared to surgery in the treatment of insulinomas. However, a randomized controlled trial to ...

6. 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 ...

7. giejournal.org giejournal.org/article/S0016-5107(23)00376-0/abstract

Risk factors for EUS-guided radiofrequency ablation ... The results of this large study confirm an overall acceptable safety profile for pancreatic EUS-RFA. Close proximity (≤1 mm) to the main ...