Hepatocellular Carcinoma (HCC)Phase 3DARTSNCT07027436
Radiation Therapy Followed by Durvalumab (MEDI4736) and Tremelimumab And Surgery Versus Radiation Therapy Followed by Surgery for Resectable Hepatocellular Carcinoma.
A Phase 3 study testing Chemotherapy/Radiation in people with Hepatocellular Carcinoma (HCC), run by Hamilton Health Sciences Corporation at 2 sites in Canada.
Trial summary
The objectives of this study is to estimate the biological activity of combination chemotherapy and radiation versus radiation alone in patients with Hepato Cellular Carcinoma (HCC). The study hypothesizes is that combination chemotherapy and radiation is superior to radiation alone in inducing a biological response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma (HCC)
- What is being tested?
- Chemotherapy/Radiation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesCanada
- Study dates
- 7 Nov 2025to 10 Oct 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Radiologically or biopsy proven solitary HCC without biliary invasion or metastases, Liver Imaging Reporting and Data Systems (LI- RADS) 4 or 5 only. Participants with satellite tumour nodules are eligible. Satellitosis or a satellite nodule is defined as a tumour (LI-RADS 4 or 5 only) less than or equal to 2 cm and located less than or equal to 2 cm from the main tumour.
- Tumour less than 12 cm in maximum size on CT or MRI.
- Planned surgical resection of HCC with a life expectancy of at least 12 weeks
- Age >18 years at time of study entry.
- Child-Pugh Class A within 14 days prior to study enrollment
- Eastern Cooperative Oncology Group (ECOG) of 0 or 1 (see Appendix 3)
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- Body weight >30 kg at time of study enrollment
- Adequate normal organ and marrow function as defined below:
- Haemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC ≥1.0 × 109 /L)
- Platelet count ≥75 × 109/L
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN).
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
- Males:
- Creatinine CL (mL/min) = Weight (kg) x (140 - Age)72 x serum creatinine (mg/dL)
- Females:
- Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
- Patient is capable and willing to provide signed informed consent.
Who cannot join
- Previous therapy for HCC, including systemic therapy, surgery, radiation therapy, ablation or embolization.
- 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.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Previous radiation therapy or surgery within 4 weeks of the randomization.
- Previous allogenic organ transplantation
- Previous anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapy
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- Previous receipt of durvalumab and / or tremelimumab or allergy to it
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy except for alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- History of active primary immunodeficiency
- Conditions that would preclude administration of durvalumab and / or tremelimumab
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Patients with a past or resolved HBV infection (defined as the presence of antiHBc and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- b.1. Patients co-infected with HBV and HCV or co-infected with HBV and HDV, namely: HBV positive (presence of HBsAg and/or anti HBcAb with detectable HBV DNA); and
- b.2. HCV positive (presence of anti-HCV antibodies); or
- b.3. HDV positive (presence of anti-HDV antibodies)
- b.4. Patients with HBV infection, characterized by positive HBsAg and/or anti-HBcAb with undetectable HBV DNA (< 10 IU/ml or under the limit of detection per local lab standard) do not require antiviral therapy prior to enrollment. These patients will be tested once for HBV DNA levels; if HBV DNA is detected (≥ 10 IU/ml or above the limit of detection per local lab standard), antiviral therapy must be initiated, continued for the study duration and for 6 months after the last dose of IP.
- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) which is not well controlled or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
- c.1. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load for 3 months, CD4+ count of >200 no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 3 months on the same anti-HIV medications.
- History of another primary malignancy, except for
- Malignancy treated with curative intent and with no known active disease ≥2 years before randomization and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Current or prior use of immunosuppressive medication within 14 days before enrollment. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to enrollment. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 90 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab and tremelimumab combination therapy.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 1 recruiting
- Recruiting
Juravinski Hospital
Hamilton, Ontario, L8V 1C3
Pablo E Serrano, PhD, MD, 9055212100 ext. 43872, serrano@mcmaster.ca
- Active, not recruiting
London Health Sciences Centre
London, Ontario, N6A 5W9
About this study
Official title: Radiation Therapy Followed by Durvalumab (MEDI4736) and Tremelimumab And Surgery Versus Radiation Therapy Followed by Surgery for Resectable Hepatocellular Carcinoma. A Randomized Window of Opportunity Trial (DARTS)
The objectives of this study is to estimate the biological activity of combination chemotherapy and radiation versus radiation alone in patients with Hepato Cellular Carcinoma (HCC).
The study hypothesizes is that combination chemotherapy and radiation is superior to radiation alone in inducing a biological response. The study hypothesizes that combination chemotherapy and radiation is superior to radiation alone in inducing a biological response. A biological response, or change in the tumor microenvironment (TME), is defined by reduced infiltration of intra-tumoral regulatory T cells (Tregs), a decrease in tumour-associated macrophages (TAMs) of the M2 phenotype, and an increase in immune cells such as effector CD8+ T-cells. An increased rate of biological response is therefore expected in participants receiving the combination of Durvalumab, Tremelimumab, and stereotactic body radiation therapy (SBRT), compared to those receiving SBRT alone. Additionally, biological response is hypothesized to correlate with pathological response.
The study has been conducted within a WOO window of opportunity randomized clinical trial in order to obtain data in the quickest and safest manner. Patients undergoing surgery are very healthy by definition and will be able to tolerate treatment without any major complications, leading to adequate tissue samples before and after treatment.
- Conditions
- Hepatocellular Carcinoma (HCC)
- Being tested
- Chemotherapy/Radiation
- Keywords
- Durvalumab/tremelimumab, SBRT, radiation, HCC, WOO, Window of Opportunity
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemotherapy/RadiationDrug
Also called Group 1
Combination of radiation and chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| SBRT and Chemotherapy | Experimental | 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. Receives: Drug: Chemotherapy/Radiation |
| SBRT alone | No intervention | The patients receive radiation only without chemotherapy SBRT prior to the surgery. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intratumoral immune cells (regulatory T lymphocytes or Tregs).
This will be measured pre and post treatment through proteomic analysis with digital spatial profiling (DSP) technology. This will determine with high resolution the area of infiltration (tumour versus stroma), to assess the relative immune status of the tumor (i.e., hot or cold). The primary endpoint is the percentage change in Tregs in the TME. The percentage change in Tregs is defined as the: (number of Tregs at surgery) / (number of Tregs at baseline) *100%.
Measured: Baseline and immediately after the intervention
Secondary outcomes (5)
Intratumoural immune cells including M2-TAMs measured similarly to the primary outcome measure.
measured similarly to the primary outcome measure.
Measured: Baseline and immediately after the intervention
Intratumoural immune cells
Intratumoural immune cells (such as B cells, CD8+ T cells)
Measured: Baseline and immediately after the intervention
TMB
which will be defined as the number of somatic nonsynonymous mutations or variants present in the coding region expressed as mutations per megabase (muts/Mb) of sequence. TMB will be measured using DNA/RNA seq, which will be analysed in the specimen pre- treatment. RNA seq will be analysed post treatment using ThermoFisher's Oncomine Comprehensive Assay Plus Assay (DNA-seq) and ThermoFisher's Ion AmpliSeqTM Transcriptome Human Gene Expression Kit (RNA-seq).
Measured: Baseline and immediately after the intervention
PD-L1 expression
PD-L1 expression before and after treatment will be performed using immunohistochemistry in the specimen
Measured: Baseline and immediately after the intervention
The percent change in peripheral blood immune repertoire.
TCR-sequencing using ThermoFisher's Oncomine TCR Beta-LR Assay: changes in the immune repertoire produced by therapy will be analysed in peripheral blood using DNA from the buffy coat at baseline and post treatment. Relevant T cell clonotypes will be identified through TCR analysis of the resected tumour.
Measured: Baseline and immediately after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2025
- Study start7 Nov 2025
- Primary completion12 Oct 2027 (estimated)
- Study completion10 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamilton Health Sciences Corporation
- Sponsor type
- University, hospital or other
- Collaborators
- McMaster University, London Health Sciences Centre
- Responsible party
- Principal investigator, Pablo Serrano, Hamilton Health Sciences Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07027436
- Sponsor's protocol ID
- DARTS ESR-23-22174
- Other IDs
- ESR-23-22174
- Acronym
- DARTS
- Status last verified
- Sep 2026
- First submitted
- 3 Jun 2025
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiation Therapy Followed by Durvalumab (MEDI4736) and Tremelimumab And Surgery Versus Radiation Therapy Followed by Surgery for Resectable Hepatocellular Carcinoma. A Randomized Window of Opportunity Trial (DARTS)
- ClinicalTrials.gov ID
- NCT07027436
- Acronym / sponsor ID
- DARTS / DARTS ESR-23-22174
- Conditions
- Hepatocellular Carcinoma (HCC)
- Keywords
- Durvalumab/tremelimumab, SBRT, radiation, HCC, WOO, Window of Opportunity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hamilton Health Sciences CorporationUniversity, hospital or other
- Collaborators
- McMaster University, London Health Sciences Centre
- Study start
- 7 Nov 2025 (actual)
- Primary completion
- 12 Oct 2027 (estimated)
- Study completion
- 10 Oct 2028 (estimated)
- First posted
- 18 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this study is to estimate the biological activity of combination chemotherapy and radiation versus radiation alone in patients with Hepato Cellular Carcinoma (HCC).
The study hypothesizes is that combination chemotherapy and radiation is superior to radiation alone in inducing a biological response. The study hypothesizes that combination chemotherapy and radiation is superior to radiation alone in inducing a biological response. A biological response, or change in the tumor microenvironment (TME), is defined by reduced infiltration of intra-tumoral regulatory T cells (Tregs), a decrease in tumour-associated macrophages (TAMs) of the M2 phenotype, and an increase in immune cells such as effector CD8+ T-cells. An increased rate of biological response is therefore expected in participants receiving the combination of Durvalumab, Tremelimumab, and stereotactic body radiation therapy (SBRT), compared to those receiving SBRT alone. Additionally, biological response is hypothesized to correlate with pathological response.
The study has been conducted within a WOO window of opportunity randomized clinical trial in order to obtain data in the quickest and safest manner. Patients undergoing surgery are very healthy by definition and will be able to tolerate treatment without any major complications, leading to adequate tissue samples before and after treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SBRT and Chemotherapy | Experimental | Drug: Chemotherapy/RadiationStudy 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. |
| SBRT alone | No intervention | –The patients receive radiation only without chemotherapy SBRT prior to the surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Radiologically or biopsy proven solitary HCC without biliary invasion or metastases, Liver Imaging Reporting and Data Systems (LI- RADS) 4 or 5 only. Participants with satellite tumour nodules are eligible. Satellitosis or a satellite nodule is defined as a tumour (LI-RADS 4 or 5 only) less than or equal to 2 cm and located less than or equal to 2 cm from the main tumour.
- Tumour less than 12 cm in maximum size on CT or MRI.
- Planned surgical resection of HCC with a life expectancy of at least 12 weeks
- Age >18 years at time of study entry.
- Child-Pugh Class A within 14 days prior to study enrollment
Key exclusion criteria (36 listed)
- Previous therapy for HCC, including systemic therapy, surgery, radiation therapy, ablation or embolization.
- 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.
- Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Previous radiation therapy or surgery within 4 weeks of the randomization.
- Previous allogenic organ transplantation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemotherapy/RadiationAlso: Group 1Combination of radiation and chemotherapy | Drug | SBRT and Chemotherapy |
Primary outcome
Intratumoral immune cells (regulatory T lymphocytes or Tregs).
Time frame: Baseline and immediately after the intervention
This will be measured pre and post treatment through proteomic analysis with digital spatial profiling (DSP) technology. This will determine with high resolution the area of infiltration (tumour versus stroma), to assess the relative immune status of the tumor (i.e., hot or cold). The primary endpoint is the percentage change in Tregs in the TME. The percentage change in Tregs is defined as the: (number of Tregs at surgery) / (number of Tregs at baseline) *100%.
5 secondary outcomes
Intratumoural immune cells including M2-TAMs measured similarly to the primary outcome measure.
Time frame: Baseline and immediately after the intervention
Intratumoural immune cells
Time frame: Baseline and immediately after the intervention
TMB
Time frame: Baseline and immediately after the intervention
PD-L1 expression
Time frame: Baseline and immediately after the intervention
The percent change in peripheral blood immune repertoire.
Time frame: Baseline and immediately after the intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chemotherapy/Radiation in people with Hepatocellular Carcinoma (HCC), run by Hamilton Health Sciences Corporation at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intratumoral immune cells (regulatory T lymphocytes or Tregs). (time frame: Baseline and immediately after the intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.