Pembrolizumab + Radiotherapy for Liver Cancer

Overseen By Jennifer J. Knox, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Organ transplant, Autoimmune disease, 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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression or intolerable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining pembrolizumab, an immune therapy, with stereotactic body radiotherapy (SBRT), a focused form of radiation, for individuals with advanced liver cancer. It targets those whose liver cancer has worsened despite previous treatment with sorafenib. The trial aims to determine if this new combination can better manage the cancer. Suitable candidates have liver cancer unresponsive to sorafenib and a liver suitable for targeted radiation, with no more than 10 tumors that are not too large. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment.

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

Research has shown that combining pembrolizumab with stereotactic body radiotherapy (SBRT) is generally safe and well-tolerated. One study on this combination for advanced liver cancer found it could be administered safely. While some side effects occurred, they were manageable. Common side effects included tiredness and skin reactions, typical for cancer treatments.

SBRT has also effectively controlled tumor growth in the liver. It targets cancer cells more precisely, helping to protect healthy tissues. This precision makes it a safer option for patients.

Pembrolizumab is already FDA-approved for other cancer types, indicating that the drug's safety is well-understood, although individual experiences with side effects can differ. Patients should always discuss potential risks and benefits with their healthcare provider before joining any trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for liver cancer, such as surgery, traditional chemotherapy, and targeted therapies like sorafenib, the combination of pembrolizumab with stereotactic body radiotherapy (SBRT) offers a novel approach. Pembrolizumab is an immunotherapy that works by blocking the PD-1 pathway, helping the immune system recognize and attack cancer cells more effectively. SBRT precisely targets tumors with high doses of radiation over a short period, potentially minimizing damage to surrounding healthy tissue. Researchers are excited about this combo because it could enhance the immune response while also directly targeting and shrinking tumors, offering a potentially more effective and less invasive treatment option for liver cancer patients.

What evidence suggests that pembrolizumab and SBRT might be an effective treatment for liver cancer?

Research has shown that pembrolizumab, a drug that boosts the immune system, combined with stereotactic body radiotherapy (SBRT), a precise type of radiation treatment, may help treat advanced liver cancer. This trial will evaluate the combination of pembrolizumab and SBRT, which studies suggest could control the cancer by strengthening the body's natural defenses against tumors. SBRT already effectively manages liver tumors, and when used with pembrolizumab, it might enhance the overall treatment effect. Early results indicated that this combination can be safe and possibly more effective than using each treatment alone. This approach aims to target the cancer more precisely and help the immune system fight it. ^{1 2 4 6 7}

Who Is on the Research Team?

Jennifer J. Knox, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

Adults with advanced liver cancer (hepatocellular carcinoma) who have seen their disease progress after sorafenib treatment. They must be in good liver function (Child Pugh Class A), have no more than 10 treatable tumors within the liver, and no tumor larger than 15 cm. Participants need to provide a biopsy, not have had certain prior treatments or conditions like brain metastases or active hepatitis B and C together, and agree to use contraception if of childbearing potential.

Inclusion Criteria

Willing and able to provide written informed consent/assent for the trial

No single liver tumor >15 cm in diameter

Smaller satellites of HCC or non-definite HCC need not be encompassed within SBRT volumes if needed to respect normal tissue limits

Exclusion Criteria

You experienced bleeding from the esophagus or stomach within the past 3 months before joining the study.

You have received a specific type of radiation therapy called radioembolization or other selective internal radiotherapy treatment to the liver in the past.

Has a histological or cytological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma-HCC

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Pembrolizumab administered intravenously every 21 days, with stereotactic radiotherapy starting on day 2 of the first cycle, delivered in 5 fractions over 8-15 days

Until disease progression or intolerable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment, with re-evaluation for response every 12 weeks

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Stereotactic Body Radiotherapy (SBRT)

Trial Overview The trial is testing the effectiveness of combining pembrolizumab, an immunotherapy drug, with stereotactic body radiotherapy (SBRT) for treating advanced hepatocellular carcinoma. It's a phase 2 study where all participants receive both treatments to see how well they work together after previous sorafenib therapy has failed.

How Is the Trial Designed?

Group I: Pembrolizumab and Stereotactic Body Radiotherapy (SBRT) Experimental Treatment 2 Interventions

Pembrolizumab, intravenously, at a dose of 200 mg, once every 3 weeks SBRT starting Day 2 of Cycle 1 of pembrolizumab treatment, given in 5 fractions over 10-15 days.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2589555925003404

Pembrolizumab and stereotactic body radiotherapy ... The PEMRAD phase II trial investigated the combination of pembrolizumab and stereotactic body radiation (SBRT) in patients with advanced HCC ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03316872

Study of Pembrolizumab and Radiotherapy in Liver Cancer This is a phase 2 study whose purpose is to assess the efficacy of the combination of pembrolizumab and stereotactic body radiotherapy (SBRT) in patients with ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7340168/

Long term outcomes of Stereotactic Body Radiation Therapy ... This report aimed to address the limited availability of long-term outcomes post SBRT for HCC from North America.

4. redjournal.org redjournal.org/article/S0360-3016(24)00007-5/abstract

Combined Stereotactic Body Radiation Therapy and ... Stereotactic body radiation therapy (SBRT) safely and effectively controls liver metastases (LMs), but its safety and efficacy when combined with immune ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12165918/

Stereotactic body radiation therapy (SBRT) increases anti ... Stereotactic body radiation therapy (SBRT) increases anti-PD-1 antitumor activity by enhancing the tumor immune microenvironment in mice with metastatic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11095610/

Survival Outcome Analysis of Stereotactic Body ... Preclinical data showed that SBRT could modulate the tumor micro-environment, prime the immune system, and work synergistically with the checkpoint inhibitors [ ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12487014/

Efficacy and safety of stereotactic body radiotherapy for ... We sought to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma with tumor thrombus in ...