Pressure-enabled Drug Delivery for Liver Cancer

(PEDIR Trial)

Not currently recruiting at 1 trial location

Overseen By Patrick D Sutphin, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Chemotherapy, Radiotherapy, Hepatic encephalopathy, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best method to deliver treatment to liver cancer tumors using two different catheter systems. It seeks to determine if the Pressure Enabled Drug Delivery (PEDD) system improves radiation delivery directly to tumors compared to a standard microcatheter. Participants will undergo both catheter procedures to evaluate which is more effective. This trial may suit individuals with liver cancer that cannot be surgically removed or treated with other methods and who are already planning to undergo radioembolization, a specific type of radiation treatment. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance future treatment options.

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 have had chemotherapy or radiotherapy within 4 to 6 weeks before joining the study.

What prior data suggests that these devices are safe for use in liver cancer treatment?

Research shows that the Pressure Enabled Drug Delivery (PEDD) system and TriNav Infusion System are generally safe and well-tolerated by patients. Studies have demonstrated that the TriNav system effectively delivers treatment to liver tumors while protecting healthy liver tissue, targeting cancer and minimizing harm to surrounding areas.

Although specific data on side effects from these studies is not available, the ongoing use of the PEDD system suggests it is considered safe for further testing. However, discussing potential risks with the study team is important to understand what participation might involve.

In summary, research supports the PEDD system's effectiveness and indicates it is safe to use, but like any medical procedure, there can be risks. Always consult healthcare providers to get the full picture. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to deliver treatments directly to liver tumors using a pressure-enabled drug delivery (PEDD) device. Unlike traditional methods that rely on standard microcatheters, the PEDD device may enhance the precision and effectiveness of radioembolization therapy by optimizing the delivery of therapeutic agents to the tumor site. This approach could potentially improve outcomes for patients with hepatocellular carcinoma (HCC) or colorectal liver metastases by ensuring more targeted and efficient treatment.

What evidence suggests that these devices are effective for improving radioactivity delivery in liver cancer?

Research has shown that the Pressure-Enabled Drug Delivery (PEDD) system can significantly enhance liver cancer treatment. One study found that PEDD increased the amount of treatment reaching tumors by 227% compared to traditional methods. This increase means more medicine reaches the cancer cells, potentially making the treatment more effective. In this trial, participants will undergo different sequences of mapping procedures using either the PEDD device or a standard microcatheter. A review of 61 liver cancer patients demonstrated that PEDD improved the precision of treatment targeting tumors, which is crucial for success. This method shows promise for treating both hepatocellular carcinoma and cancer that has spread to the liver. ^{1 4 5 6 7}

Who Is on the Research Team?

Patrick D Sutphin, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults with liver cancer or colorectal metastases to the liver, who can't have surgery or thermal ablation. They should be in relatively good health (ECOG <2), with a life expectancy over 16 weeks and adequate organ function. Participants must not be pregnant, nursing, or planning to conceive soon. Those with stable extrahepatic disease may qualify.

Inclusion Criteria

Hemoglobin: ≥ 8.5 g/dL

My organs and bone marrow are working well.

I can do most of my daily activities by myself.

Exclusion Criteria

I have had radiation or specific artery treatments to my liver before.

More than half of my liver is affected by cancer.

I have received treatment for a condition affecting the Ampulla of Vater.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Mapping Procedure

Participants undergo a mapping procedure to evaluate blood supply to the liver and tumor using angiography and radiotracer injection

2-21 days before treatment

1 visit (in-person)

Radioembolization Treatment

Participants receive radioembolization treatment with an additional mapping procedure on the treatment day

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PEDD device
• Standard microcatheter

Trial Overview The study is testing whether using a Pressure Enabled Drug Delivery (PEDD) device during mapping for radioembolization improves treatment delivery to liver tumors compared to a standard microcatheter.

How Is the Trial Designed?

Group I: Sequence B: PEDD device for Mapping #1 and standard microcatheter for Mapping #2. Experimental Treatment 2 Interventions

Participants with either hepatocellular carcinoma (HCC) or colorectal liver metastases tumors receiving standard of care radioembolization treatment will be randomly assigned to undergo a routine mapping procedure first using the PEDD device catheter 2-21 days before their radioembolization treatment day. Then on day of radioembolization treatment, an extra mapping procedure using a standard microcatheter will be done just prior to the treatment.

Group II: Sequence A: Standard microcatheter for Mapping #1 and PEDD device for Mapping #2. Experimental Treatment 2 Interventions

Participants with either hepatocellular carcinoma (HCC) or colorectal liver metastases tumors receiving standard of care radioembolization treatment will be randomly assigned to undergo a routine mapping procedure first using a standard microcatheter 2-21 days before their radioembolization treatment day. Then on day of radioembolization treatment, an extra mapping procedure using the PEDD device catheter will be done just prior to the treatment.

PEDD device is already approved in United States for the following indications:

Approved in United States as TriNav Infusion System for:

• Liver cancer

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

TriSalus Life Sciences, Inc.

Industry Sponsor

Trials

10

Recruited

420+

TriSalus Life Sciences

Collaborator

Trials

5

Recruited

70+

Published Research Related to This Trial

Antireflux microcatheters (ARMs) are a new type of microcatheter that can enhance liver-directed therapies like selective internal radiotherapy (SIRT) and trans-arterial chemoembolization (TACE) by reducing particle reflux and improving drug delivery to tumors.

Using ARMs may lead to better particle distribution and embolization efficiency, potentially resulting in improved disease response for patients with liver cancers, particularly hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Surefire's precision direct-to-tumor embolization device to augment therapeutic response to intra-arterial, liver-directed therapies for patients with primary and secondary liver cancers. Kim, AY., Miller, A.[2019]

A new model for hepatic arterial chemotherapy using large dogs and an implantable infusion pump allows for over 90% perfusion of the liver, making it a reliable method for studying liver-targeted treatments.

The implantation of the pump does not cause acute liver damage or affect the dogs' mobility, indicating its safety for use in preclinical studies of chemotherapeutic agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dog model using an implanted system for protracted hepatic arterial chemotherapy. Wollner, IS., Knutsen, CA., Ullrich, KA., et al.[2019]

A totally implanted drug delivery system for hepatic arterial chemotherapy was successfully evaluated in 13 patients, showing reliable performance with stable flow rates and excellent patient acceptance over a median treatment duration of 6 months.

The system led to partial tumor regressions in 11 out of 13 patients, indicating its efficacy in delivering chemotherapy directly to liver tumors, while allowing patients to maintain normal daily activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Totally implanted drug delivery system for hepatic arterial chemotherapy. Ensminger, W., Niederhuber, J., Dakhil, S., et al.[2013]

The coaxial reservoir system with a non-braided microcatheter was successfully implanted in 100% of the 80 patients, demonstrating its efficacy for hepatic arterial infusion chemotherapy.

While the system is generally safe, there were some complications, including a 10% rate of hepatic arterial occlusion, indicating that while effective, careful monitoring is necessary during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic arterial infusion chemotherapy with a coaxial reservoir system using a non-braided spiral tip microcatheter. Koganemaru, M., Abe, T., Iwamoto, R., et al.[2021]

A new implantable port design allows for easy insertion of a microcatheter, enabling repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer.

In both in vitro and in vivo studies, the port demonstrated successful catheterization and repeated selective embolization in a pig model, indicating its potential effectiveness for ongoing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Repeatable Microcatheter Access Port for Intra-arterial Therapy of Liver Cancer. Fukuoka, Y., Tanaka, T., Nishiofuku, H., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05128032

Pressure-enabled Delivery in Radioembolization (TriNav ... The purpose of the study is to determine if the type of catheter used in the mapping procedure prior to radioembolization improves the delivery of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1051044324007206

Pressure-Enabled Drug Delivery Significantly Increases ... PEDD increased microsphere penetration into the tumor by 227% (P = .029) when compared with conventional methodology and improved the tumor–to–normal tissue ...

3. trinavinfusion.com trinavinfusion.com/wp-content/uploads/22-Clinical-Summary-dAbadie-Study-R01.pdf

Pressure-Enabled Drug Delivery™ Improves Tumor Targeting ... SUMMARY: A retrospective analysis of 61 patients with liver cancer (190 lesions) treated with resin Y90 radioembolization (RE) showed that Pressure-Enabled ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/03007995.2024.2322057

Real-world evidence of Pressure-Enabled Drug Delivery ... A method using pressure to advance catheter-delivered drug distribution, can improve treatment for hepatocellular carcinoma (HCC) and liver metastases.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12536300/

Pressure enabled drug delivery (PEDD) of nelitolimod ... Pressure enabled drug delivery (PEDD) of nelitolimod increased therapeutic delivery, reduced immunosuppression, and improved efficacy in porcine ...

6. investors.trisaluslifesci.com investors.trisaluslifesci.com/news-releases/news-release-details/trisalus-life-sciencesr-announces-publication-pre-clinical-data

Release Details Results showed the TriNav Infusion System using the PEDD approach markedly outperforms traditional microcatheters in delivering embolic ...

7. trinavinfusion.com trinavinfusion.com/pedd-evidence/

PEDD Evidence - TriNav Infusion System The TriNav Infusion System was shown to significantly increase tumor penetration of embolic microspheres with improved sparing of normal liver tissue. ... Kapoor ...