Ipilimumab + Nivolumab with SBRT for Liver Cancer

Overseen By Yoko Takahashi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Hawaii

Must not be taking: Corticosteroids, others

Disqualifiers: Prior systemic therapy, Hypertension, GI bleeding, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for liver cancer that cannot be removed by surgery. It combines two immunotherapy drugs, ipilimumab and nivolumab, with a targeted form of radiation therapy called SBRT. The aim is to determine if this approach can enable surgery and improve survival. The trial focuses on Native Hawaiian and Pacific Islander patients, who experience higher rates of liver cancer and have fewer treatment options. Patients with liver cancer characterized by certain tumor sizes or locations that complicate surgery might be suitable candidates for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using nivolumab and ipilimumab with SBRT (a precise type of radiation therapy) is generally well-tolerated by patients with liver cancer. Studies have found that this treatment can extend the lives of those with advanced liver cancer.

The safety of this combination is considered manageable, meaning that while some side effects may occur, they are usually not serious and can be treated with proper care. Common side effects include fatigue, skin rash, and changes in liver function tests, but these are often mild and temporary.

The U.S. Food and Drug Administration (FDA) has approved nivolumab and ipilimumab for certain liver cancer cases, indicating confidence in the safety of this treatment for this type of cancer. Although this approval applies to different situations, it suggests that the treatment is generally safe.

Overall, evidence suggests that this treatment is safe enough to consider joining a trial. It is important to consult a healthcare provider to understand what this could mean specifically for an individual. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Ipilimumab and Nivolumab with SBRT for liver cancer because it takes a novel approach to treating this tough condition. Unlike the standard treatments, which often involve surgery or traditional chemotherapy, this combo uses two immunotherapy drugs that help the immune system recognize and attack cancer cells. Additionally, the use of stereotactic body radiotherapy (SBRT) allows for precise targeting of tumors, potentially increasing the effectiveness while minimizing damage to surrounding healthy tissue. This approach not only boosts the body's own defenses but also offers hope for patients who might not be eligible for surgery, presenting a promising alternative to current methods.

What evidence suggests that this trial's treatments could be effective for liver cancer?

In this trial, participants will receive a combination of ipilimumab and nivolumab, with some also receiving stereotactic body radiotherapy (SBRT). Research has shown that using ipilimumab and nivolumab together can effectively combat liver cancer, particularly in advanced cases. Specifically, studies have found that patients with inoperable liver cancer lived longer with this treatment, averaging a survival time of 23.7 months. SBRT effectively controls the cancer, achieving a 95% success rate over five years. These treatments together aim to improve patient outcomes and may enable surgery for those previously not considered candidates. Early evidence suggests this combination could extend patient survival and increase the likelihood of surgery becoming an option. ^{1 2 3 4 5}

Who Is on the Research Team?

Jared D Acoba, MD

Principal Investigator

University of Hawaii

Are You a Good Fit for This Trial?

This trial is for individuals with advanced liver cancer, specifically hepatocellular carcinoma (HCC), who are part of the Native Hawaiian and Pacific Islander populations. It's aimed at those with borderline resectable disease, meaning surgery alone isn't enough. Participants should not have had prior treatments that would conflict with the study.

Inclusion Criteria

Measurable disease per RECIST 1.1

My liver cancer diagnosis was confirmed through lab tests.

My liver cancer is advanced but might be removable with surgery.

Exclusion Criteria

I have had treatment for liver cancer before.

My cancer has spread directly into nearby organs.

I haven't had radiation on over 30% of my bone marrow in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Immunotherapy

Participants receive ipilimumab and nivolumab for nine weeks (three cycles) to assess resectability

9 weeks

3 visits (in-person)

Surgical Resection

Eligible patients undergo surgical resection following imaging to confirm resectability

Up to 12 weeks from treatment initiation

Continued Immunotherapy and SBRT

Patients not eligible for resection continue immunotherapy and receive stereotactic body radiotherapy

Varies based on resectability confirmation

Imaging every 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The trial tests a combination of two immune checkpoint inhibitors, Ipilimumab and Nivolumab, along with Stereotactic Body Radiotherapy (SBRT). The goal is to see if this mix can make surgery possible and improve survival rates in patients typically considered inoperable due to their advanced HCC.

How Is the Trial Designed?

Group I: Ipilimumab and Nivolumab with SBRT and Surgical Resection Experimental Treatment 2 Interventions

Arm A: Patients receive ipilimumab 3mg/kg and nivolumab 1mg/kg for nine weeks (three cycles). Following completion of preoperative immunotherapy, imaging with CT or MRI is performed to determine resectability. Eligible patients proceed to surgical resection. Arm B: Patients who are not eligible for resection continue immunotherapy (ipilimumab and nivolumab) for one additional cycle, then nivolumab 480mg every four weeks combined with stereotactic body radiotherapy (SBRT). SBRT is administered in 3-5 fractions, and patients continue imaging every nine weeks. Surgical resection is performed once resectability is confirmed.

Who Is Running the Clinical Trial?

University of Hawaii

Lead Sponsor

Trials

122

Recruited

55,200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11910043/

Efficacy and Safety of Ipilimumab Plus Anti-PD-1/PD-L1 ... The combination of nivolumab and ipilimumab has demonstrated significant antitumor activity in first-line treatment for hepatocellular carcinoma ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)00082-6/fulltext

Nivolumab plus ipilimumab combination therapy in patients ... The median follow-up (time from randomization to data cutoff) was 62.6 months (range 60-69 months) for all randomized patients in this study.

3. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(25)02471-7/fulltext

Nivolumab plus ipilimumab for potentially resectable ... This study evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with potentially resectable HCC and explored predictive ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00403-9/fulltext

Nivolumab plus ipilimumab versus lenvatinib or sorafenib ... Nivolumab plus ipilimumab showed a significant overall survival benefit versus lenvatinib or sorafenib and manageable safety in patients with ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma

FDA approves nivolumab with ipilimumab for unresectable ... Median OS was 23.7 months (95% CI: 18.8, 29.4) in the nivolumab + ipilimumab arm and 20.6 months (95% CI: 17.5, 22.5) in the lenvatinib or ...