Surefire Infusion System for Liver Cancer

Recruiting in Boston (>99 mi)

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

Trial Summary

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 data supports the idea that Surefire Infusion System for Liver Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of the Surefire Infusion System for Liver Cancer. The studies mentioned focus on doxorubicin, a drug used in various forms for cancer treatment, but they do not directly address liver cancer or the Surefire Infusion System. Some studies discuss the use of doxorubicin in other cancers, like colorectal and ovarian cancer, but they do not show significant effectiveness in those cases. Therefore, there is no direct evidence from the provided information to support the effectiveness of the Surefire Infusion System for Liver Cancer. ^{1 2 3 4 5}

What safety data is available for the Surefire Infusion System treatment for liver cancer?

The safety data for doxorubicin, which is used in the Surefire Infusion System, includes various formulations such as conventional and liposomal doxorubicin. Conventional doxorubicin is associated with risks like myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting. Liposomal formulations, such as PEGylated and non-PEGylated liposomal doxorubicin, generally show lower risks of myelosuppression, cardiotoxicity, and alopecia compared to conventional doxorubicin. However, liposomal formulations, especially PEGylated ones, have a higher risk of palmar-plantar erythrodysesthesia (PPE). Pegylated liposomal doxorubicin is generally well tolerated, with some patients experiencing leucopenia, stomatitis, and PPE. Myocet, a non-PEGylated liposomal formulation, reduces toxicities associated with soluble doxorubicin but has some formulation drawbacks. Overall, liposomal encapsulation aims to increase safety by reducing cardiac and gastrointestinal toxicity. ^{3 4 6 7 8}

Is the drug Doxorubicin a promising treatment for liver cancer?

Yes, Doxorubicin shows promise as a treatment for liver cancer. It can be delivered directly to the liver, which helps concentrate the drug where it's needed and reduces side effects. This method has shown positive responses in some patients, improving their survival time. ^{1 9 10 11 12}

What is the purpose of this trial?

This research study is studying the TriNav ("TriSalus") for increasing delivery of chemotherapeutic agents delivered trans-arterially to intermediate stage Hepatocellular Carcinoma ("HCC") (Barcelona Clinic Liver Cancer (BCLC) class B; locally advanced, liver restricted disease patients. The names of the study interventions involved in this study are: -Trans-arterial chemoembolization ("TACE") with or without the utilization of Surefire

Research Team

Dmitry Rabkin, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

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

My liver cancer cannot be removed by surgery and a team of experts recommends TACE.

Exclusion Criteria

Patients who cannot undergo MRI evaluation/examination

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

Pregnant or breastfeeding women

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. England 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. [2018]

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

Phase II study of liposomal doxorubicin in patients with advanced colorectal cancer. [2019]

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

Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome Production. [2018]

4. England 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. [2019]

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

Liposome drug delivery system for murine neuroblastoma. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Safety aspects of pegylated liposomal doxorubicin in patients with cancer. [2018]

7. United States 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. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Synthesis, characterization, and cytotoxicity of doxorubicin-loaded polycaprolactone nanocapsules as controlled anti-hepatocellular carcinoma drug release system. [2022]

10. Germany 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. [2018]

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

A clinical-pharmacological evaluation of percutaneous isolated hepatic infusion of doxorubicin in patients with unresectable liver tumors. [2013]

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

Reduction of systemic drug exposure after hepatic arterial infusion of doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration. [2013]