TACE + SBRT for Liver Cancer

(TACE Trial)

Overseen By Michael Lock, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Disqualifiers: Severe cirrhosis, Liver failure, Pregnancy, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two treatments—TACE (a method delivering chemotherapy directly to the liver) and SBRT (a precise form of radiation therapy)—is more effective than TACE alone in controlling liver cancer. The trial targets patients with liver cancer or liver tumors that have spread from other cancers. Suitable candidates include those diagnosed with liver cancer, with up to five liver tumors visible on scans, and whose cancer cannot be surgically removed. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, chemotherapy must be completed at least 2 weeks before starting radiation therapy or TACE, and it should not be planned for at least 1 week after treatment (4 weeks for certain drugs).

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

Research has shown that Transarterial Chemoembolization (TACE) is usually well-tolerated. Studies indicate it can extend life while controlling side effects, meaning most people don't experience severe reactions.

Stereotactic Body Radiation Therapy (SBRT) also maintains a good safety record. It effectively manages liver cancer with generally manageable side effects. Reports suggest that SBRT is both practical and safe.

Both treatments have been studied and found safe for many patients. While no treatment is without risk, evidence suggests these therapies are generally well-tolerated by most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Transarterial Chemoembolization (TACE) with Stereotactic Body Radiation Therapy (SBRT) for liver cancer because it offers a novel approach that targets tumors more precisely and effectively. Unlike traditional treatments, which often involve surgery or systemic chemotherapy, this combination focuses directly on the liver tumor, potentially enhancing the precision of the attack on cancer cells. TACE works by delivering chemotherapy directly to the liver tumor while blocking its blood supply, and SBRT adds a high dose of radiation with pinpoint accuracy. This dual approach aims to maximize tumor control while minimizing damage to healthy tissue, promising better outcomes and fewer side effects for patients.

What evidence suggests that TACE plus SBRT could be effective for liver cancer?

Studies have shown that Transarterial Chemoembolization (TACE), a treatment available in this trial, can be very effective for liver cancer. In one study, 96% of patients had no detectable cancer after treatment, though the cancer can sometimes return. Stereotactic Body Radiation Therapy (SBRT) is another option in this trial, and research indicates that SBRT can successfully control liver cancer for up to five years without severe side effects. This trial will also test the combination of TACE with SBRT, which could potentially enhance long-term cancer control. ^{1 2 3 5 6}

Who Is on the Research Team?

Michael Lock, M.D.

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Are You a Good Fit for This Trial?

This trial is for adults with liver cancer, having up to 5 liver lesions and no severe cirrhosis or active hepatitis. They must not have had certain treatments recently, be able to use contraception, and have a life expectancy over 6 months. Those with larger tumors or previous radiation in the same area can't join.

Inclusion Criteria

Life expectancy > 6 months.

My liver cancer can be treated with TACE.

All my liver cancer can be targeted with radiation.

Exclusion Criteria

I have had radiation in the same area where my current cancer is located.

My liver is not severely damaged (Child Pugh ≤ B7).

My health issues do not limit my life expectancy to under 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Transarterial Chemoembolization (TACE) or TACE plus Stereotactic Body Radiation Therapy (SBRT)

6 weeks

Weekly visits during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

1 and 3 month follow-up, and every 3 months thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic Body Radiation Therapy
• Transarterial Chemoembolization

Trial Overview The study compares standard TACE treatment for liver cancer against TACE combined with SBRT, a precise radiation therapy. It aims to see if adding SBRT better controls the growth of liver tumors after TACE.

How Is the Trial Designed?

Group I: Transarterial Chemoembolization (TACE) Active Control 1 Intervention

Transarterial Chemoembolization (TACE)

Group II: TACE Plus Stereotactic Body Radiation Therapy (SBRT) Active Control 1 Intervention

Stereotactic Body Radiation Therapy (SBRT)

Transarterial Chemoembolization is already approved in United States, China, European Union for the following indications:

Approved in United States as TACE for:

• Non-small cell lung cancer
• Lung metastases

Approved in China as TACE for:

• Unresectable lung cancer
• Advanced lung cancer

Approved in European Union as TACE for:

• Non-small cell lung cancer
• Lung metastases

Who Is Running the Clinical Trial?

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

CancerCare Manitoba

Collaborator

Trials

29

Recruited

5,600+

Published Research Related to This Trial

In a meta-analysis of 9 studies involving 938 patients, the combination of stereotactic body radiotherapy (SBRT) and transcatheter arterial chemoembolization (TACE) significantly improved 1-year and 2-year overall survival rates compared to either treatment alone for patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT).

The combination therapy also resulted in a higher objective response rate and a lower progression disease rate, with no significant increase in adverse events compared to monotherapy, suggesting it is a safe and effective treatment option for inoperable HCC patients with PVTT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy plus transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma patients with portal vein tumour thrombus: A meta-analysis. Zhang, XF., Lai, L., Zhou, H., et al.[2022]

In a study of 49 patients receiving transarterial chemoembolization (TACE) combined with stereotactic body radiation therapy (SBRT), overall survival rates were significantly better compared to 98 patients receiving TACE alone, with 1-year survival rates of 67.2% versus 43.9%.

The combination of TACE and SBRT also improved progression-free survival rates and radiological disease control, while showing a low risk of severe treatment-related toxicity, indicating it is a safe and effective option for patients with nonresectable hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Better survival after stereotactic body radiation therapy following transarterial chemoembolization in nonresectable hepatocellular carcinoma: A propensity score matched analysis. Wong, TC., Chiang, CL., Lee, AS., et al.[2019]

A meta-analysis of 10 studies involving 980 patients found that combining stereotactic body radiotherapy (SBRT) with transcatheter arterial chemoembolization (TACE) significantly improves overall survival and disease control rates compared to SBRT alone for treating unresectable hepatocellular carcinoma (HCC).

While the combination therapy (SBRT + TACE) showed better efficacy, it was associated with a higher incidence of leukopenia and fever, indicating the need for careful monitoring of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiotherapy Combined with Transcatheter Arterial Chemoembolization versus Stereotactic Body Radiotherapy Alone as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review. Zhao, J., Zeng, L., Wu, Q., et al.[2020]

In a study of 168 patients with hepatocellular carcinoma who underwent 305 transarterial chemoembolization (TACE) procedures, biliary complications occurred in only 3.6% of patients, indicating that such complications are infrequent.

The types of biliary complications included minimal intrahepatic biliary dilatation, biliary stricture, and intrahepatic biloma, with treatment varying based on severity, highlighting the importance of clinical suspicion and imaging for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biliary complications of arterial chemoembolization of hepatocellular carcinoma. Dhamija, E., Paul, SB., Gamanagatti, SR., et al.[2015]

In a study of 190 patients with inoperable hepatocellular carcinoma (HCC), transarterial chemoembolization combined with thermal ablation (TACE-TA) resulted in significantly better overall survival (77% at 2 years) and progression-free survival (76% at 2 years) compared to TACE with stereotactic body radiotherapy (TACE-SBRT), which had 49% and 50% respectively.

TACE-TA also demonstrated lower rates of treatment-related hepatotoxicity (9%) compared to TACE-SBRT (27%), suggesting that TACE-TA may be a safer option for patients, although both treatments showed similar outcomes for patients with early-stage HCC and preserved liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thermal Ablation Versus Stereotactic Body Radiotherapy After Transarterial Chemoembolization for Inoperable Hepatocellular Carcinoma: A Propensity Score-Weighted Analysis. Nabavizadeh, N., Jahangiri, Y., Rahmani, R., et al.[2021]

In a study of 103 patients with unresectable hepatocellular carcinoma, combining drug eluting bead transarterial chemoembolization (DEB-TACE) with stereotactic body radiation therapy (SBRT) resulted in a high objective response rate, with 62.1% achieving a complete response and 26.3% a partial response.

Patients who received planned adjuvant SBRT after DEB-TACE had significantly better outcomes compared to those who received salvage SBRT, suggesting that this combination therapy could be an effective strategy for improving local control and overall survival in liver cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy following transarterial chemoembolization for unresectable hepatocellular carcinoma. Buckstein, M., Kim, E., Fischman, A., et al.[2022]

In a pilot study of 28 patients with small hepatocellular carcinoma (HCC), the combination of transcatheter arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) achieved a remarkable 1-year local tumor control rate of 96.3%.

The treatment was found to be safe, with no severe acute toxicity reported, and resulted in a median disease-free survival of 18 months and a 1-year overall survival rate of 92.6%, indicating its efficacy as a locoregional therapy for small HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. Honda, Y., Kimura, T., Aikata, H., et al.[2022]

In a study of 68 patients with small, solitary, hypervascular hepatocellular carcinoma (HCC), combining stereotactic body radiation therapy (SBRT) with transcatheter arterial chemoembolization (TACE) resulted in a complete response in 96.3% of patients, compared to only 3.3% in the TACE-only group, highlighting the efficacy of the combination treatment.

The combination therapy was found to be safe, with no patients experiencing severe acute hematologic toxicity or radiation-induced liver damage, and it significantly improved disease-free survival (15.7 months vs 4.2 months) for patients without previous HCC treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. Honda, Y., Kimura, T., Aikata, H., et al.[2022]

In a study of 57 patients with BCLC stage B hepatocellular carcinoma, the combination of trans-arterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) resulted in a high objective response rate of 85.9% and a local control rate of 91.1% at one year, indicating strong efficacy for this treatment approach.

The treatment was well tolerated, with only 1.8% of patients experiencing severe gastrointestinal toxicity, suggesting that TACE followed by SBRT is a safe option for patients who cannot undergo surgery or radiofrequency ablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Prognostic Factors of Trans-Arterial Chemoembolization Combined With Stereotactic Body Radiation Therapy for BCLC Stage B Hepatocellular Carcinoma. Jiang, C., Jing, S., Zhou, H., et al.[2022]

In a study of 72 patients with advanced hepatocellular carcinoma (HCC), combining trans-arterial chemoembolization (TACE) with stereotactic body radiotherapy (SBRT) resulted in a high objective response rate of 68% and a 1-year local control rate of 93.6%.

The treatment was found to be safe, with only 2.8% of patients experiencing severe gastrointestinal side effects and no cases of classical radiation-induced liver injury, suggesting that this combination therapy can be a viable initial treatment option for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B-C hepatocellular carcinoma. Chiang, CL., Chan, MKH., Yeung, CSY., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12460054

Stereotactic body radiotherapy with CyberKnife for liver ... The pooled 3-year LC and OS rates were 82.5% (95% confidence interval [CI], 75.0%–90.0%) and 58.7% (95% CI, 47.2%–70.1%), respectively, which is ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001551

Long-term outcomes of more than a decade treating ... SBRT resulted in a 5-year LC of 95% in the treatment of primary liver cancer (HCC). •. No SBRT related ≥ grade 3 toxicity was reported. •. Treatment outcomes of ...

3. redjournal.org redjournal.org/article/S0360-3016(23)07777-5/fulltext

Stereotactic Body Radiation Therapy for Hepatocellular ... This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2512-x

Clinical outcomes and prognostic factors of cyberknife ... Cyberknife SBRT appears to be an effective non-invasive treatment for local unresectable HCC with low risk of severe toxicity.

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

Long term outcomes of Stereotactic Body Radiation Therapy ... While transplant and surgical resection are associated with five-year survival rates of approximately 66%, a minority of patients are eligible for liver ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001691

Stereotactic body radiation therapy in primary liver tumor SBRT provides good LC with an acceptable safety profile. It can be used in several settings such as salvage therapy or in combination with validated treatment.