Cryoablation + SD-101 for Liver Cancer

Overseen By Isabel Newton, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Diego

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Brain metastases, Cardiac impairment, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 9

20 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, if you are using immunosuppressive medications, you must stop them 14 days before starting the trial, unless they are certain types of steroids or at low doses.

What data supports the effectiveness of the treatment Cryoablation + SD-101 for Liver Cancer?

Research shows that cryoablation, a treatment that freezes cancer cells, is relatively safe and effective for liver cancer, especially when combined with other therapies like chemotherapy or immunotherapy. This suggests that combining cryoablation with other treatments, such as SD-101, could potentially enhance its effectiveness for liver cancer. ^{1 2 3 4 5}

Is cryoablation safe for treating liver cancer?

Studies show that cryoablation, a procedure that freezes and destroys cancer cells, is generally safe for treating liver cancer, with research focusing on its safety and effectiveness in various settings. ^{3 4 5 6 7}

How does the treatment Cryoablation + SD-101 for liver cancer differ from other treatments?

Cryoablation is a unique treatment for liver cancer that involves freezing the tumor to destroy it, which can be done without major surgery and is particularly useful for patients who cannot undergo traditional surgery. It also has the potential to trigger an immune response against the cancer. The combination with SD-101, an investigational drug, may enhance this immune response, making it a novel approach compared to standard treatments. ^{2 3 5 8 9}

What is the purpose of this trial?

The goal of this Phase 1b clinical trial is to evaluate the safety and efficacy of cryoablation and hepatic arterial administration of SD-101 in participants with advanced hepatocellular carcinoma. After this procedure, participants will be treated with tremelimumab and durvalumab every 4 weeks (STRIDE regimen).

Research Team

Adam Burgoyne, MD, PhD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for adults with advanced liver cancer who are in good physical condition and haven't had previous systemic treatments for their cancer. They must have a tumor that's at least 3 cm away from sensitive areas, can't be candidates for local therapies like surgery or radiation, and should have acceptable liver function (Child-Pugh A or B7).

Inclusion Criteria

I am willing and able to sign a consent form for the study.

My cirrhosis diagnosis is confirmed clinically as per AASLD guidelines.

My liver cancer diagnosis follows international guidelines.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cryoablation and SD-101 Administration

Participants undergo ultrasound- and/or CT-guided cryoablation of a hepatic lesion and concurrent administration of SD-101

1 week

1 visit (in-person)

Treatment with STRIDE Regimen

Participants receive tremelimumab and durvalumab every 4 weeks

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Every 8 weeks (in-person)

Treatment Details

Interventions

• Durvalumab
• SD-101
• Tremelimumab

Trial Overview The study tests the combination of cryoablation (freezing of the tumor) and SD-101 injected into the liver artery followed by immunotherapy drugs tremelimumab and durvalumab every four weeks to see if they're safe and effective against advanced hepatocellular carcinoma.

Participant Groups

Group I: SD-101 Experimental Treatment 4 Interventions

Participants will be treated with cryoablation and intrahepatic artery infusion of SD-101. This treatment will be followed by administration of the immune checkpoint inhibitors Tremelimumab and Durvalumab (STRIDE regimen). Tremelimumab 300mg will be given intravenously once, 7-10 days after cryoablation + SD-101. Durvalumab 1500mg will be given intravenously at the same time as Tremelimumab, and then every 28 days (on day 1 of every subsequent cycle).

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

TriSalus Life Sciences

Collaborator

Trials

5

Recruited

70+

TriSalus Life Sciences, Inc.

Industry Sponsor

Trials

10

Recruited

420+

Findings from Research

In a study of 78 patients with unresectable hepatocellular carcinoma (HCC), the combination of cryoablation and sorafenib showed promising efficacy, with a median overall survival of 12.2 months and a median time to progression of 6.6 months.

The treatment was well-tolerated, with 43.6% of patients achieving stable disease and 11.5% showing partial responses, indicating that this combination therapy is a viable option for patients with advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib combined with cryoablation to treat unresectable hepatocellular carcinoma. Ni, H., Yang, M., Guo, Z., et al.[2021]

Cryoablation is a promising treatment for unresectable liver cancers, such as hepatocellular carcinoma (HCC), as it can be performed using various methods (percutaneously, intraoperatively, and laparoscopically) and is relatively safe and efficient based on preliminary research.

This technique not only effectively induces tumor necrosis through iceball formation but also has minimal impact on surrounding blood vessels and can trigger a cryo-immunological response, making it a potential alternative treatment option when combined with other therapies like radiation and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Cryoablation for Liver Cancer. Niu, LZ., Li, JL., Xu, KC.[2022]

Percutaneous cryoablation for liver metastases from breast cancer showed a high technical success rate of 92% and an effectiveness rate of 87.1% at one month after treatment, indicating it is a promising option for local tumor control.

The procedure was found to be safe, with no major complications reported, and it preserved quality of life in patients, as evidenced by stable symptoms and functioning scales at three months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoablation of liver metastases from breast cancer: initial experience in 17 patients. Zhang, W., Yu, H., Guo, Z., et al.[2015]

In a study of 143 patients undergoing liver tumor cryoablation, factors such as larger tumor size (≥4 cm), low pre-procedural platelet count (<100,000/μL), and prior local radiation therapy were identified as independent risk factors for reduced overall survival.

Interestingly, the occurrence of grade 3 or higher adverse events during the cryoablation procedure did not correlate with decreased survival, suggesting that the procedure itself may be safe in terms of long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periprocedural factors associated with overall patient survival following percutaneous image-guided liver tumor cryoablation. Daye, D., Hu, EY., Glazer, DI., et al.[2022]

Cryoablation (CA) is a safe and effective treatment for liver cancer located near critical structures, with a 100% technical success rate in 69 procedures performed on 66 patients, and no serious complications reported.

The cumulative local tumor progression rates were relatively low at 6 months (10.2%) and increased to 30.5% by 24 months, indicating that while some tumors may progress, CA effectively controls tumor growth in the short to medium term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoablation for the treatment of liver cancer at special sites: an assessment of efficacy and safety. Ma, J., Wang, F., Zhang, W., et al.[2022]

The study demonstrated that percutaneous cryoablation guided by CT is safe and feasible, as all seven pigs survived the procedure without complications or serious hemorrhage.

Cryoablation effectively created ice balls that corresponded well with areas of tissue necrosis, indicating that this method could be a reliable technique for targeting tumors in the liver.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CT-monitored percutaneous cryoablation in a pig liver model: pilot study. Lee, FT., Chosy, SG., Littrup, PJ., et al.[2016]

Percutaneous cryoablation of renal tumors smaller than 7 cm has a low overall complication rate of 8.3%, indicating it is a safe treatment option for patients.

Tumors larger than 4 cm are associated with a higher risk of major complications, highlighting the importance of tumor size in assessing treatment risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of percutaneous renal cryoablation: an international multicentre experience from the EuRECA retrospective percutaneous database. Garnon, J., Van Strijen, MJ., Nielsen, TK., et al.[2020]

The new cryoprobe allows for effective percutaneous cryoablation of small liver tumors, with a study involving 15 patients showing no complications and stable liver function post-procedure.

Cryoablation was successful in achieving complete response in 6 cases and partial response in 5 cases, but the method is recommended primarily for tumors smaller than 3 cm due to limitations in the size of the ice ball created during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Percutaneous cryosurgery for liver tumors]. Nakazaki, H., Watanabe, M., Hasebe, Y., et al.[2006]

Cryoablation is a safe and effective treatment for primary and metastatic liver tumors, particularly for patients at higher risk for major surgery, such as older adults or those with pre-existing liver conditions, as demonstrated in a study of 28 patients with 39 tumors.

Despite its safety, cryoablation has a high recurrence rate at the treated site (19%), indicating that while it can be a palliative option, it may not provide long-term disease-free survival, and careful patient selection is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Realistic expectations for cryoablation of liver tumors. Helling, TS.[2019]

References

1. China pubmed.ncbi.nlm.nih.gov

Sorafenib combined with cryoablation to treat unresectable hepatocellular carcinoma. [2021]

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

Percutaneous Cryoablation for Liver Cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Percutaneous cryoablation of liver metastases from breast cancer: initial experience in 17 patients. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Periprocedural factors associated with overall patient survival following percutaneous image-guided liver tumor cryoablation. [2022]

5. China pubmed.ncbi.nlm.nih.gov

Percutaneous cryoablation for the treatment of liver cancer at special sites: an assessment of efficacy and safety. [2022]

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

CT-monitored percutaneous cryoablation in a pig liver model: pilot study. [2016]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety of percutaneous renal cryoablation: an international multicentre experience from the EuRECA retrospective percutaneous database. [2020]

8. Japan pubmed.ncbi.nlm.nih.gov

[Percutaneous cryosurgery for liver tumors]. [2006]

9. Japan pubmed.ncbi.nlm.nih.gov

Realistic expectations for cryoablation of liver tumors. [2019]