Surefire Infusion System for Liver Cancer

Overseen By Dmitry Rabkin, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Dana-Farber Cancer Institute

Disqualifiers: Prior local therapy, Brain metastases, Hepatic decompensation, Severe cardiac/renal diseases, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for delivering chemotherapy to treat liver cancer, specifically intermediate stage Hepatocellular Carcinoma (HCC), where the cancer remains confined to the liver but cannot be surgically removed. Researchers aim to determine if using the TriNav system (also known as the Surefire Infusion System) to deliver chemotherapy directly to the liver is more effective than traditional methods. Participants will receive chemotherapy either with the new TriNav system or the traditional method. This trial may suit individuals whose liver cancer is inoperable, has not spread beyond the liver, and who have not undergone prior regional treatments like surgery or radiation. As a Phase 4 trial, this research seeks to understand how the already FDA-approved treatment benefits more patients.

Do I have to stop taking my current medications for the trial?

The protocol does not specify if you need to stop taking your current medications. However, prior systemic chemotherapy is allowed, so you might not need to stop all medications. It's best to discuss your specific medications with the trial team.

What is the safety track record for these treatments?

Research has shown that the Surefire Infusion System, when combined with doxorubicin, is generally safe for patients. One study reported no serious side effects beyond mild to moderate ones, indicating that any side effects were not severe. Previous research also found that patients tolerated the treatment well, without major problems.

The Surefire Infusion System delivers chemotherapy directly to liver tumors, potentially enhancing treatment effectiveness while maintaining safety. Overall, evidence suggests that using this system with doxorubicin is safe based on past patient experiences. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for liver cancer because they explore different delivery methods of the chemotherapy drug, Doxorubicin, during a TACE procedure. Unlike the traditional delivery method, the Surefire Infusion System uses a device called TriNav, which is designed to precisely target the tumor, potentially increasing the effectiveness of the treatment and minimizing damage to healthy tissues. This targeted delivery could improve patient outcomes by enhancing the concentration of the drug in the tumor while reducing side effects.

What evidence suggests that the Surefire Infusion System is effective for liver cancer?

In this trial, participants will receive Doxorubicin for liver cancer through one of two delivery methods. Research has shown that the Surefire Infusion System, one of the methods tested, can enhance Doxorubicin's effectiveness. In some studies, patients experienced a complete response, with significant tumor shrinkage. A large study involving over 100 patients found that the Surefire system was safe and effective for treating liver tumors. It is designed to deliver chemotherapy drugs directly to the tumor more efficiently than traditional methods. This approach could help the medicine reach the cancer more effectively, potentially improving results for patients with liver cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Dmitry Rabkin, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with unresectable intermediate stage Hepatocellular Carcinoma (HCC) who haven't had previous regional liver treatments. They should have a life expectancy of over 12 months, acceptable blood counts and organ function, and be able to consent. Pregnant women or those with severe heart, kidney diseases, HIV, brain metastases or certain other conditions are excluded.

Inclusion Criteria

Negative pregnancy test required due to significant radiation exposure during the procedure

Ability to understand and sign a written informed consent document

Life expectancy of at least 12 months

Exclusion Criteria

Patients who cannot undergo MRI evaluation/examination

Pregnant or breastfeeding women

My liver cancer has blocked the main vein without causing other veins to enlarge.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single administration of intra-arterial chemotherapy (Doxorubicin) during the TACE procedure via either TriNav or Traditional Delivery

1 day

1 visit (in-person)

Follow-up

Participants undergo structural follow-up with contrast-enhanced MRI to assess tumor response

1 year

Regular intervals for MRI

Long-term monitoring

Participants are monitored for secondary outcome measures such as capillary permeability and plasma volume

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Doxorubicin
• Surefire Infusion System
• Traditional Delivery

Trial Overview The study tests the Surefire Infusion System's effectiveness in delivering chemotherapy directly to liver tumors during Trans-arterial chemoembolization (TACE). It compares TACE with and without Surefire in patients with locally advanced HCC that can't be surgically removed.

How Is the Trial Designed?

Group I: TACE Procedure With TriNav Experimental Treatment 2 Interventions

Patients will receive a single administration of intra-arterial chemotherapy (Doxorubicin) during the TACE procedure via TriNav. * Patients will undergo structural follow-up for a timeframe of one year post treatment * Post-procedural, contrast-enhanced Magnetic Resonance Imaging (MRI) will be performed one month after trial entry, and at regular intervals thereafter for a total of one year to assess tumor response

Group II: TACE Procedure Traditional Delivery Active Control 2 Interventions

Patients will receive a single administration of intra-arterial chemotherapy (Doxorubicin) during the TACE procedure via Traditional Delivery. * Patients will undergo structural follow-up for a timeframe of one year post treatment * Post-procedural, contrast-enhanced Magnetic Resonance Imaging (MRI) will be performed one month after trial entry, and at regular intervals thereafter for a total of one year to assess tumor response

Doxorubicin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Adriamycin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in European Union as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Canada as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Japan as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Published Research Related to This Trial

The study involved 18 patients with unresectable liver tumors and demonstrated that hepatic arterial infusion of doxorubicin can achieve high intrahepatic concentrations, ranging from 30 to 88 microg/ml, while maintaining a consistent hepatic extraction ratio of 60.3%.

At doses of 90 and 120 mg/m2, the treatment showed a dose-response effect, with a median overall survival of 23 months for responders compared to 8 months for nonresponders, indicating the efficacy of this method in treating advanced hepatic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical-pharmacological evaluation of percutaneous isolated hepatic infusion of doxorubicin in patients with unresectable liver tumors. Hwu, WJ., Salem, RR., Pollak, J., et al.[2013]

Electrospray manufacturing of Myocet-like liposomes allows for a more efficient and scalable production process, enhancing drug retention and stability compared to traditional thin-film hydration methods.

The electrosprayed liposomes demonstrated similar drug loading and cytotoxicity profiles to conventional formulations, but with significantly prolonged release kinetics, potentially improving therapeutic outcomes for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome Production. Collier, MA., Bachelder, EM., Ainslie, KM.[2018]

Doxorubicin (Dox) was successfully encapsulated in biodegradable polycaprolactone (PCL) nanocapsules, which showed a high encapsulation efficiency of 73.15% and a faster drug release rate in acidic cancer conditions (98%) compared to normal physiological conditions (26%).

The Dox-PCL nanocapsules demonstrated reduced toxicity to normal cells while exhibiting a significantly higher cytotoxic effect on HepG2 cancer cells compared to free Dox, suggesting a safer and more targeted approach for treating hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis, characterization, and cytotoxicity of doxorubicin-loaded polycaprolactone nanocapsules as controlled anti-hepatocellular carcinoma drug release system. Fahmi, A., Abdur-Rahman, M., Mahareek, O., et al.[2022]

This study analyzed over 7.5 million reports from the FDA Adverse Event Reporting System and found that conventional doxorubicin (DOX) has a higher incidence of adverse events compared to liposomal formulations, particularly in terms of myelosuppression and cardiotoxicity.

Liposomal DOX, especially the PEGylated version, showed lower reporting odds ratios for serious side effects like myelosuppression and cardiotoxicity, but a higher risk for palmar-plantar erythrodysesthesia (PPE), indicating the need for careful monitoring when using these formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. Fukuda, A., Tahara, K., Hane, Y., et al.[2022]

In a trial involving 17 patients with advanced colorectal cancer, Doxil (a liposomal formulation of doxorubicin) was well tolerated, with manageable side effects such as hand-foot syndrome and mild allergic reactions.

Despite being well tolerated, Doxil did not show significant efficacy in this patient group, as none achieved a partial response, and the best outcome was stable disease, suggesting that further research is needed to explore its effectiveness in other cancers responsive to doxorubicin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of liposomal doxorubicin in patients with advanced colorectal cancer. Shields, AF., Lange, LM., Zalupski, MM.[2019]

Pegylated liposomal doxorubicin is generally well tolerated in patients with solid tumors, with lower rates of severe side effects like alopecia and cardiotoxicity compared to traditional doxorubicin, as shown in a phase II trial for refractory ovarian cancer.

While it reduces some adverse effects, pegylated liposomal doxorubicin may increase the risk of mucositis, and ongoing studies are exploring optimal dosing and safety when combined with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety aspects of pegylated liposomal doxorubicin in patients with cancer. Alberts, DS., Garcia, DJ.[2018]

In a phase I study involving 18 patients with various solid tumors, liposomal encapsulation of doxorubicin (Myocet) demonstrated a longer half-life and reduced exposure of free doxorubicin to healthy tissues, which may enhance safety and tolerability.

The study found that while common side effects included nausea and fatigue, serious cardiotoxicity was rare, with only one patient experiencing a significant drop in heart function, indicating a favorable safety profile for Myocet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study. Mross, K., Niemann, B., Massing, U., et al.[2021]

Liposome-infused doxorubicin (Lip-DXR) significantly increased survival time in mice with C-1300 murine neuroblastoma, extending it to an average of 43.86 days compared to 31.40 days for standard doxorubicin (DXR) and 27 days for the control group.

The use of Lip-DXR resulted in lower concentrations of doxorubicin in cardiac tissues, suggesting a reduced risk of cardiac toxicity compared to the standard DXR treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposome drug delivery system for murine neuroblastoma. Nagae, I., Koyanagi, Y., Ito, S., et al.[2019]

The study found that the generic doxorubicin liposome injection developed by Sun Pharmaceuticals (SPIL) has a plasma and tissue distribution profile that is generally comparable to the reference product, Caelyx®, in murine models.

Minor differences in tissue distribution were noted, but these variations were likely due to biological differences rather than significant discrepancies between the two formulations, suggesting that SPIL's product may offer a similar benefit-risk profile as Caelyx®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. Burade, V., Bhowmick, S., Maiti, K., et al.[2018]

In a study comparing 40 patients treated with Lipodox® to 120 matched patients treated with Doxil®, Lipodox® showed a significantly lower overall response rate of 4.3% compared to 18% for Doxil®, indicating reduced efficacy in treating recurrent ovarian cancer.

Despite similar toxicity profiles between Lipodox® and Doxil®, the lack of equivalent efficacy suggests that further prospective clinical studies are needed before Lipodox® can be considered a suitable substitute for Doxil®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it equivalent? Evaluation of the clinical activity of single agent Lipodox® compared to single agent Doxil® in ovarian cancer treatment. Smith, JA., Costales, AB., Jaffari, M., et al.[2019]

The novel venous isolation-chemofiltration system significantly reduced systemic exposure to doxorubicin by over 90% after hepatic arterial infusion in a study involving domestic pigs, indicating a potential way to minimize toxic side effects.

This system allowed for a 16-fold increase in doxorubicin levels in the liver compared to the heart, suggesting it could enable higher doses of the drug to be safely administered for treating liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of systemic drug exposure after hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration. Curley, SA., Byrd, DR., Newman, RA., et al.[2013]

The proposed generic doxorubicin hydrochloride liposome injection (SPIL) demonstrated comparable antitumor efficacy to the reference product (Caelyx) in mouse models, significantly reducing tumor volume without significant differences in effectiveness at any tested dose.

Both SPIL and the reference injection exhibited similar toxicity profiles and pharmacokinetics, confirming their bioequivalence and supporting the development of affordable cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models. Burade, V., Bhowmick, S., Maiti, K., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02853500

Effect of Surefire Infusion Device on Tumor Response to ... Investigators are doing this research to determine if a TriNav Infusion System can improve tumor response to liver-directed intra-arterial chemotherapy compared ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5580978/

Short-term imaging response after drug-eluting embolic ... Twenty-two patients with 39 hepatocellular carcinoma lesions were treated with the surefire infusion system. Complete response was demonstrated ...

3. trinavinfusion.com trinavinfusion.com/wp-content/uploads/MKT-0508_Clinical-Summary_DEB-TACE-Registry-V1.0.pdf

Clinical Summary: A Multi-Center Registry Study of the Safety ... 133 Surefire Infusion System (SIS) hepatocellular carcinoma registry study interim results: a multi- center study of the safety, feasibility, and outcomes ...

4. trisaluslifesci.com trisaluslifesci.com/wp-content/uploads/2025/01/TLSI-corporate-deck-011425-Final-2.pdf

January 2025 system successfully treats complex liver cancer patients1 ... hepatocellular carcinoma, pancreatic cancer, and other solid liver tumors.

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

Real-world evidence of Pressure-Enabled Drug Delivery ... Surefire Infusion System (SIS) hepatocellular carcinoma registry study interim results: a multicenter study of the safety, feasibility, and outcomes of the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03170869

Bridge to Orthotopic Liver Transplantation (OLT) - Surefire ... The purpose of this study will be to prospectively evaluate the outcomes of patients with hepatocellular carcinoma (HCC) who undergo DEB-TACE (drug-eluting bead ...