IP-001 for Liver Cancer

Overseen By Robert Martin, MD, PhD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an experimental treatment called IP-001 to determine if it can help people with liver cancer remain cancer-free longer after surgery or a procedure to remove the tumor. It targets individuals with liver cancer confined to the liver who are at a higher risk of recurrence. Participants should plan to undergo surgery or ablation (a treatment that destroys cancer cells with heat) and should not have had other recent liver treatments. The trial will compare the effects of receiving IP-001 after surgery or ablation to not receiving it. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in liver cancer treatment.

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.

Is there any evidence suggesting that IP-001 is likely to be safe for humans?

Research has shown that IP-001 was well-tolerated in early human studies, which included patients with advanced melanoma and soft tissue cancers. Although specific side effects are not detailed, the ongoing testing of IP-001 suggests it has not caused serious safety issues. The liver cancer trial is in Phase 2, building on earlier research to examine safety and how the body processes the treatment. This phase indicates initial evidence that IP-001 is safe enough for further testing in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver cancer?

Unlike the standard treatments for liver cancer, which often involve surgery or local ablation alone, IP-001 introduces an innovative approach by combining these methods with a targeted injection. This treatment is unique because it uses a 1.0% solution of IP-001 administered immediately after local ablation or surgical resection, which aims to enhance the effectiveness of the initial procedure. Researchers are excited about IP-001 because it could potentially improve outcomes by directly targeting residual cancer cells that might remain after the primary treatment, offering a promising new layer of defense against liver cancer recurrence.

What evidence suggests that IP-001 might be an effective treatment for liver cancer?

In this trial, participants will receive either IP-001 or a control treatment. Research has shown that IP-001, when used after treatments like ablation (a method that destroys cancer cells) for liver cancer, might help the body's immune system fight cancer more effectively. One study found that using IP-001 with thermal ablation slowed tumor growth more than other treatments. This suggests that IP-001 could enhance the immune system's ability to combat cancer by increasing the activity of immune cells in the tumor area. This promising effect arises because IP-001 may boost both the body's natural and learned immune responses. While more research is needed, these findings offer hope for IP-001's potential in treating liver cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Robert CG Martin, MD, PhD

Principal Investigator

University of Louisville

Are You a Good Fit for This Trial?

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.

Known allergic reaction to shellfish, crabs, crustacean, or any trial components

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-2-hepatocellular-carcinoma-6-2024-5413f

IP-001 for Liver Cancer 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06526338

Adjuvant IP-001 Treatment for HCC Patients Following ... 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 ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/02656736.2024.2413591

Thermal ablation enhances immunotherapeutic effect of IP ... We hypothesize that IP-001 in combination with MWA can enhance the therapeutic efficacy against HCC via an innate and adaptive immune response.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39389594/

Thermal ablation enhances immunotherapeutic effect of IP ... Results: IP001 + MWA treatment significantly suppressed tumor growth in comparison to the other 3 groups. Significantly increased infiltration ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2949819823000055

Immune checkpoint inhibition (ICI) in current systemic ... Immune checkpoint inhibitors (ICI) are now standard of care in first-line treatment of hepatocellular carcinoma and show promising long-term efficacy in some ...

6. clinconnect.io clinconnect.io/trials/NCT06526338

Adjuvant IP-001 Treatment for HCC Patients Following 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 ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK559177/

Hepatocellular Carcinoma - StatPearls - NCBI Bookshelf - NIH Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology. 2016 Jul;64(1):106-16.