Radiation and Immunotherapy for Liver Cancer

(DARTS Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hamilton Health Sciences Corporation

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-CTLA-4

Disqualifiers: Autoimmune disorders, Hepatitis, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding chemotherapy to radiation treatment is more effective for liver cancer than radiation alone. It specifically examines how these treatments alter the tumor environment, aiming to reduce immune-suppressing cells and increase immune-fighting cells. Eligible participants must have a single confirmed liver cancer tumor, plan to have it surgically removed, and not have received any prior treatment for it. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot take any other cancer treatments or immunosuppressive medications within 14 days before joining the study. It's best to discuss your current medications with the study team to see if they are allowed.

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

Research shows that the combination of Durvalumab and Tremelimumab is generally well-tolerated by people with liver cancer. Studies have found that this treatment can be safe even for those with advanced stages of the disease. While side effects can occur, they are often manageable. Common side effects include tiredness, nausea, and skin reactions. Serious side effects are less common, but they can occur.

A safety study using a large database found that most patients handle this combination without severe problems. This suggests that the treatment is relatively safe, with a clear understanding of the possible risks.

This combination has undergone several stages of testing, providing extensive safety information. If the treatment is already approved for another condition, that adds to the evidence of its safety when used correctly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Stereotactic Body Radiation Therapy (SBRT) with immunotherapy drugs like Durvalumab and Tremelimumab for liver cancer because it represents a powerful new approach. Unlike traditional treatments that rely solely on chemotherapy or surgery, this method uses precise, high-dose radiation to shrink tumors, potentially making them easier to remove surgically. Additionally, the immunotherapy component helps the immune system recognize and attack cancer cells, possibly leading to longer-lasting effects. This dual-action approach could offer more effective results and fewer side effects compared to existing treatments like conventional chemotherapy and surgery alone.

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

Research has shown that combining Tremelimumab and Durvalumab with radiation can extend the lives of liver cancer patients. In this trial, one group will receive Tremelimumab and Durvalumab with Stereotactic Body Radiation Therapy (SBRT). Studies have indicated that this treatment outperformed standard treatments for patients with inoperable liver cancer. This combination enhances the immune system's ability to fight cancer and alters the tumor environment, making it easier for the body to attack the cancer. Evidence suggests that this combination therapy could be more effective than radiation alone, which is being tested in another group of this trial, for treating liver cancer. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with resectable Hepatocellular Carcinoma (HCC) who are healthy enough to undergo surgery. Participants must be able to tolerate treatment without major complications, ensuring they can provide tissue samples before and after treatment.

Inclusion Criteria

I am older than 18 years.

I am fully active or can carry out light work.

I weigh more than 30 kg.

Exclusion Criteria

Participation in another clinical study with an investigational product during the last 4 weeks or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

I have had treatments for liver cancer before.

Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) which is not well controlled or active tuberculosis infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive stereotactic body radiation therapy (SBRT) prior to surgery

1 day

1 visit (in-person)

Chemotherapy

Participants in the experimental group receive one infusion of Durvalumab and Tremelimumab

2 weeks

1 visit (in-person)

Surgery

Participants undergo surgery to obtain tissue samples for analysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Stereotactic Body Radiation Therapy (SBRT)
• Tremelimumab

Trial Overview The study compares the effects of combination chemotherapy (Durvalumab and Tremelimumab) plus radiation therapy versus radiation alone on HCC. It aims to see if the combo is better at changing the tumor environment by affecting certain immune cells.

How Is the Trial Designed?

Group I: SBRT and Chemotherapy Experimental Treatment 1 Intervention

Study participants randomized to treatment Group 1, will receive SBRT prior to surgery on Day 1, and receive one infusion of Durvalumab (1500mg IV) / Tremelimumab 300mg IV) on Day 15.

Group II: SBRT alone Active Control 1 Intervention

The patients receive radiation only without chemotherapy SBRT prior to the surgery.

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Citations

1. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2100070

Tremelimumab plus Durvalumab in Unresectable ... The primary outcome was overall survival, defined as time from date of randomization until death from any cause, for STRIDE versus sorafenib.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40222621/

Five-year overall survival update from the HIMALAYA study ... STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) vs. sorafenib in unresectable HCC and demonstrated long- ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2900049-8/fulltext

Four-year overall survival update from the phase III ... The survival rates at 18, 24, 36, and 48 months were 47.4%, 39.6%, 24.7%, and 19.3%, respectively, in the durvalumab arm. OS in the prespecified ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01462

Patient-Reported Outcomes From the Phase III HIMALAYA ... Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms.

5. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(24)02424-3/fulltext

Outcomes in the Asian subgroup of the phase III ... The global, phase III HIMALAYA study found that the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen improved overall survival ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11589085/

Early Clinical Outcomes of Durvalumab Plus ... Durvalumab plus tremelimumab may be effective and safe for unresectable hepatocellular carcinoma, even in patients who receive it as a later- ...

7. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1657398/full

A real-world drug safety surveillance study from the FAERS ... Overall, this study characterizes the adverse event profile of durvalumab plus tremelimumab in patients with HCC using the FAERS database, providing key ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4122

Sequential or up-front triple combination with durvalumab ... The MONTBLANC trial evaluates the efficacy and safety of combined durva, treme and bev in patients (pts) with aHCC.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06911255

NCT06911255 | Safety and Efficacy of Tremelimumab ... The purpose of this clinical trial is to evaluate the safety and efficacy of tremelimumab + durvalumab administered concurrently with transarterial ...