IP-001 for Liver Cancer

Recruiting in Louisville (>99 mi)

Overseen By Traci Hayat, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Robert C. Martin

Must be taking: Antivirals

Must not be taking: Immunotherapy, Chemotherapy, Glucocorticoids

Disqualifiers: Immunodeficiency, Autoimmune disease, Transplant, others

Stay on Your Current Meds You can continue your current medications while participating

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: 13

Duration: Immediate

126 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain treatments like systemic chemotherapy, biological therapy, or high-dose steroids close to the trial start. If you're on hepatitis B treatment, you should continue it during the study.

What data supports the effectiveness of the drug IP-001 for liver cancer?

The research highlights the use of immune checkpoint inhibitors (ICIs) like nivolumab and pembrolizumab, which are approved for liver cancer treatment, suggesting that similar immune-modulating treatments could be effective. Additionally, studies on combining ICIs with other therapies show promise in improving outcomes for liver cancer patients. ^{1 2 3 4 5}

What safety data exists for IP-001 in humans?

Immune checkpoint inhibitors, which may include treatments like IP-001, have been associated with liver-related side effects, such as hepatitis (liver inflammation), in some patients. These side effects have been observed in various cancer treatments, but the overall safety profile can vary depending on individual health conditions. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of a single injection of IP-001 as adjuvant therapy after local ablation or surgical resection and ablation in patients with hepatocellular carcinoma (HCC).

Research Team

Robert CG Martin, MD, PhD

Principal Investigator

University of Louisville

Eligibility Criteria

This trial is for individuals with hepatocellular carcinoma (HCC), a type of liver cancer, who have undergone surgical removal and/or local ablation of the tumor. Specific eligibility details are not provided.

Inclusion Criteria

I have completed treatment for hepatitis C at least 1 month ago.

I have been diagnosed with liver cancer through imaging or biopsy.

I am scheduled for a procedure to remove or destroy my tumor completely.

Exclusion Criteria

I am currently being treated for an infection.

I am not on high-dose steroids or have an immune deficiency.

I had a liver treatment other than radiofrequency or microwave ablation less than 3 months ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single injection of IP-001 as adjuvant therapy following local ablation or surgical resection and local ablation

Immediate

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with radiological assessments every 12 weeks for the first 2 years, then every 24 weeks thereafter

60 months

Every 12 weeks for 2 years, then every 24 weeks

Treatment Details

Interventions

• IP-001

Trial Overview The study is testing the safety and effectiveness of a single injection called IP-001 as an additional treatment after either local tumor destruction or surgery plus local destruction in HCC patients.

Participant Groups

Group I: IP-001 Experimental Treatment 3 Interventions

1.0% IP-001 for injection immediately following local ablation or surgical resection and local ablation

Group II: Control Active Control 2 Interventions

Local ablation or surgical resection and local ablation alone

Who Is Running the Clinical Trial?

Robert C. Martin

Lead Sponsor

Trials

3

Recruited

200+

Findings from Research

Immune checkpoint inhibitors (ICIs) like nivolumab and pembrolizumab are currently approved for treating hepatobiliary cancers, including hepatocellular carcinoma (HCC) and biliary tract cancer, showing efficacy in advanced stages of these diseases.

Ongoing phase III clinical trials are exploring the use of ICIs in combination with other treatments, which could significantly change the treatment landscape for liver cancers in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatobiliary cancers and immunotherapy: where are we now and where are we heading? Zayac, A., Almhanna, K.[2023]

In a review of 74 studies involving 9001 patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI), the median overall survival (OS) was found to be 13.20 months, indicating a significant treatment effect.

The study revealed that progression-free survival (PFS) is a potential surrogate for OS, especially in patients receiving combination therapies, with a strong correlation (rs = 0.79), suggesting that early endpoints like PFS can help predict long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis. Xu, H., Cao, D., Zheng, Y., et al.[2022]

Recent advances in hepatobiliary cancer research emphasize the use of immunotherapy combined with other treatments earlier in the disease progression, which may improve patient outcomes.

The focus on individualized biomarkers could help predict which patients will respond to checkpoint inhibitors, potentially leading to more effective and personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Top advances of the year: Hepatobiliary cancers. Coffman-D'Annibale, KL., Greten, TF.[2023]

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic agents showed higher efficacy in treating unresectable hepatocellular carcinoma (HCC), with an objective response rate of 26% and a disease control rate of 70% based on data from 6 randomized controlled trials involving 980 patients.

While this combination therapy improved progression-free survival and overall survival compared to monotherapy, it also led to a higher incidence of adverse events, including fatigue, hypertension, and nausea, indicating the need for careful management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of immune checkpoint inhibitors combined anti-angiogenic therapy in patients with unresectable hepatocellular carcinoma: A meta-analysis. Xian, F., Wu, C., Zhang, G., et al.[2022]

Icaritin was found to be safe for use in advanced hepatocellular carcinoma (HCC) patients, with no severe drug-related adverse events reported among the 20 participants in this phase I study.

The treatment showed promising preliminary efficacy, with 46.7% of evaluable patients experiencing clinical benefits, including one partial response and six stable disease cases, along with a median overall survival of 192 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers. Fan, Y., Li, S., Ding, X., et al.[2020]

In a study of 33 cancer patients with viral hepatitis treated with immune checkpoint inhibitors (ICIs), 39% experienced immune-related adverse events (irAEs), but only 6% had severe (grade 3 or higher) events.

Importantly, none of the patients developed hepatitis-related toxicities, suggesting that ICIs can be safely administered to patients with concurrent viral hepatitis and may be a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Viral Hepatitis: The MD Anderson Cancer Center Experience. Nardo, M., Yilmaz, B., Nelson, BE., et al.[2023]

In a study of 1480 cancer patients treated with immune checkpoint inhibitors (ICIs), over 50% experienced hepatic adverse events (AEs), with 14.9% classified as severe (grade 3-4).

The presence of hepatic AEs was linked to poorer overall survival rates, with median survival dropping from 9.0 months for patients without AEs to just 3.3 months for those with severe hepatic AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. Chan, SL., Yip, TC., Wong, VW., et al.[2021]

In a study of 2561 advanced melanoma patients treated with checkpoint inhibitors, severe hepatitis occurred in 1.8% of those on PD-1 inhibitors, 2.6% on ipilimumab, and 20.7% on combination therapy, indicating a higher risk with combined treatment.

Patients who developed checkpoint inhibitor-induced hepatitis did not show a higher prevalence of liver metastasis and their progression-free and overall survival rates were similar to those without hepatitis, suggesting that hepatitis does not negatively impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients. Biewenga, M., van der Kooij, MK., Wouters, MWJM., et al.[2021]

In a study of 406 patients with advanced hepatocellular carcinoma (HCC) receiving immune checkpoint inhibitors (ICI), the development of treatment-related adverse events (trAE) graded ≥2 was linked to significantly longer overall survival (16.7 months vs. 11.2 months) and progression-free survival (5.5 months vs. 2.2 months).

This association persisted even after adjusting for various clinical factors, indicating that trAE can serve as an independent predictor of better outcomes in HCC patients undergoing ICI therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related toxicity and improved outcome from immunotherapy in hepatocellular cancer: Evidence from an FDA pooled analysis of landmark clinical trials with validation from routine practice. Pinato, DJ., Marron, TU., Mishra-Kalyani, PS., et al.[2021]

In a study of 5,762 patients receiving immune checkpoint inhibitors (ICIs), only 2% developed significant hepatotoxicity, with a notably higher incidence in those receiving combination therapy (9.2%) compared to monotherapy (1.7%).

While most patients who experienced hepatotoxicity had to discontinue ICIs, many were able to resume treatment after liver function improved, and a majority did not experience recurrent hepatotoxicity, indicating a manageable safety profile for ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Characteristics and Adverse Impact of Hepatotoxicity due to Immune Checkpoint Inhibitors. Miller, ED., Abu-Sbeih, H., Styskel, B., et al.[2023]

References

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

Hepatobiliary cancers and immunotherapy: where are we now and where are we heading? [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Potential predictors for survival in hepatocellular carcinoma patients treated with immune checkpoint inhibitors: A meta-analysis. [2022]

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

Top advances of the year: Hepatobiliary cancers. [2023]

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

Efficacy and safety of immune checkpoint inhibitors combined anti-angiogenic therapy in patients with unresectable hepatocellular carcinoma: A meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

First-in-class immune-modulating small molecule Icaritin in advanced hepatocellular carcinoma: preliminary results of safety, durable survival and immune biomarkers. [2020]

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

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Viral Hepatitis: The MD Anderson Cancer Center Experience. [2023]

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

Pattern and impact of hepatic adverse events encountered during immune checkpoint inhibitors - A territory-wide cohort study. [2021]

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

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients. [2021]

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

Treatment-related toxicity and improved outcome from immunotherapy in hepatocellular cancer: Evidence from an FDA pooled analysis of landmark clinical trials with validation from routine practice. [2021]

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

Clinical Characteristics and Adverse Impact of Hepatotoxicity due to Immune Checkpoint Inhibitors. [2023]