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

Trial Summary

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.

What data supports the effectiveness of the treatment Endoscopic Ultrasound Radiofrequency Ablation, Neoadjuvant Chemotherapy (NAC), Pembrolizumab for pancreatic cancer?

Neoadjuvant chemotherapy (NAC) has been associated with improved survival in resectable pancreatic cancer. Pembrolizumab, an immune therapy, has shown some effectiveness in pancreatic cancer patients with high tumor mutation burden, although its overall benefit in pancreatic cancer is limited. ^{1 2 3 4 5}

Is the combination of Radiofrequency Ablation and Pembrolizumab safe for humans?

Pembrolizumab, used in various cancers, can cause immune-related side effects like inflammation of the colon, liver, lungs, kidneys, and hormone glands, and rarely, heart and blood disorders. These side effects are important to consider when evaluating its safety. ^{1 6 7 8 9}

How is the treatment of radiofrequency ablation and pembrolizumab for pancreatic cancer different from other treatments?

This treatment is unique because it combines radiofrequency ablation, which uses heat to destroy cancer cells, with pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells. This combination aims to enhance the immune response against pancreatic cancer, which is typically less responsive to immune therapies alone. ^{1 10 11 12 13}

What is the purpose of this trial?

The purpose of this study is to perform a pilot phase II trial to evaluate the safety and efficacy of combined EUS-RFA, chemotherapy, and systemic immunotherapy (pembrolizumab) for the treatment of locally advanced unresectable and metastatic Pancreatic ductal adenocarcinoma (mPDAC).

Research Team

Putao Cen

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

1. Germany 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. [2023]

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

Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer. [2022]

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

PD-1 blockade induces reactivation of non-productive T cell responses characterized by NF-kB signaling in patients with pancreatic cancer. [2023]

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

Neoadjuvant Chemotherapy versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma: An Updated Nationwide Study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Partial response to single-agent pembrolizumab in a chemotherapy-resistant metastatic pancreatic cancer patient with a high tumor mutation burden. [2023]

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

Immunogenicity of pembrolizumab in patients with advanced tumors. [2020]

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

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. [2020]

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

Immune-checkpoint inhibitor toxicity during a pandemic: Overcoming patient fears to provide care. A case report. [2022]

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

Pembrolizumab-induced thrombotic thrombocytopenic purpura. [2022]

10. New Zealand 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. [2023]

11. England 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. [2022]

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

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

13. England pubmed.ncbi.nlm.nih.gov

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