Systemic Therapy + Radiation for Liver Cancer

Overseen By Eugene Koay, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Gemcitabine, Cisplatin, Durvalumab

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Uncontrolled illness, Brain metastases, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for liver cancer that has spread beyond the liver, specifically intrahepatic cholangiocarcinoma (iCCA). Researchers aim to evaluate the effectiveness of standard cancer drugs—cisplatin, durvalumab (an immunotherapy drug), and gemcitabine—with or without added radiation therapy. Suitable participants have iCCA with a tumor larger than 3 cm that cannot be surgically removed and have already begun treatment with these drugs. The trial seeks to identify the best combination of treatments to manage the condition effectively. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take other cancer treatments besides those listed in the inclusion criteria, and you should not use immunosuppressive medications within 14 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 durvalumab, part of this trial, has been studied for safety in other contexts. Studies have found that durvalumab is generally well-tolerated. For instance, when combined with other treatments, it has helped patients with liver cancer live longer.

Regarding safety, another study found that durvalumab could be safely used again in patients who did not respond to similar treatments before. These findings suggest that durvalumab is relatively safe for liver cancer patients, although individual experiences may differ.

Cisplatin and gemcitabine are well-known chemotherapy drugs already used to treat various cancers, with known side effects. Common side effects include nausea and tiredness, but they are usually manageable.

The current trial is in phase 2, indicating some existing safety data. This phase focuses on evaluating the treatment's effectiveness and confirming its safety. While no treatment is without risk, the available data suggests that the drugs in this trial are safe enough for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they combine systemic therapy with radiation in a novel way. The experimental arm uses Liver-RT combined with Durvalumab, an immunotherapy that helps the immune system target cancer cells more effectively. This approach is distinctive because it integrates radiation with Durvalumab, potentially enhancing the immune response against the tumor. Meanwhile, the standard of care arm uses Durvalumab along with Gemcitabine and Cisplatin, two chemotherapy drugs that work together to damage the DNA of cancer cells, preventing their growth. This combination aims to maximize the destruction of cancer cells while enhancing the body's natural defenses.

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

In this trial, participants will receive different treatment combinations. One group will receive Durvalumab combined with Gemcitabine and Cisplatin. Studies have shown this combination to be promising for treating advanced biliary tract cancer, with 72% of patients experiencing a noticeable reduction in cancer size. Other research suggests that this combination can extend patient survival. Another group will receive Durvalumab combined with liver radiation therapy. Studies indicate that this combination has improved survival rates in liver cancer patients compared to other treatments. Both treatment combinations in this trial show significant potential for improving outcomes in liver cancer cases. ^{6 7 8 9 10}

Who Is on the Research Team?

Eugene Koay, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced intrahepatic cholangiocarcinoma (a type of liver cancer) who have metastatic disease at initial diagnosis. Specific eligibility criteria are not provided, but typically include factors like age, overall health status, and having no prior treatments that would conflict with the trial.

Inclusion Criteria

My cancer is advanced and cannot be removed by surgery.

Patients must meet all inclusion and have no exclusion criteria to enroll and be randomized on the study if pre-registered before cycle 4 of systemic therapy

My organs and bone marrow are functioning well.

Exclusion Criteria

Judgment by the treating physician that the patient is unsuitable to participate in the study and unlikely to comply with study procedures

Mean QT interval corrected for heart rate using Fridericia's formula ≥470 ms

Participation in another clinical study with an investigational product during the last 1 month

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care systemic therapy with or without liver-directed radiation therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Durvalumab
• Gemcitabine

Trial Overview

The study is testing the effectiveness of systemic therapy using Durvalumab combined with Gemcitabine and Cisplatin chemotherapy, comparing outcomes with or without additional liver-directed radiation therapy in patients.

How Is the Trial Designed?

Group I: Standard of Care Arm - Durvalumab + Gemcitabine + Cisplatin Experimental Treatment 3 Interventions

Participants will receive treatment in sequence with standard of care systemic therapy

Group II: Experimental Arm - Liver-RT + Durvalumab Experimental Treatment 1 Intervention

Participants will receive treatment in sequence with standard of care systemic therapy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Varian Medical Systems, Inc.

Collaborator

Trials

3

Recruited

250+

Published Research Related to This Trial

The DEDALUS phase 2 trial is investigating a new treatment approach for 45 patients with unresectable stage III non-small cell lung cancer (NSCLC), combining induction chemo-immunotherapy with de-intensified radiotherapy and the immunotherapy drug durvalumab.

The primary focus of the study is to assess safety by monitoring severe adverse events within 6 months, while secondary goals include evaluating progression-free survival (PFS) and overall survival (OS), indicating a comprehensive approach to understanding both the safety and effectiveness of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Single-Arm, Phase 2, Multi-Center Study of Chemo-Immunotherapy Followed by Hypo-Fractionated RT and Maintenance Immunotherapy in Patients With Unresectable Stage III NSCLC: The DEDALUS Trial. Filippi, AR., Agustoni, F., Arcangeli, S., et al.[2023]

In a Phase II trial involving 74 patients with unresectable, locally advanced non-small cell lung cancer (NSCLC), durvalumab immunotherapy combined with radiotherapy resulted in a promising 12-month progression-free survival (PFS) rate of 72.1%, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with a high objective response rate of 90.9%, although 52.9% of patients experienced severe adverse events (grade 3 or 4), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. Tachihara, M., Tsujino, K., Ishihara, T., et al.[2023]

In a pilot trial involving 24 patients with locally advanced unresectable hepatocellular carcinoma (HCC), the combination of Y90-radioembolization and durvalumab showed promising efficacy, with a median time to progression of 15.2 months and an overall response rate of 83.3%.

The treatment was generally safe, with 47.8% of patients experiencing any-grade treatment-related adverse events, but only 8.7% had grade 3 adverse events, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma. Lee, YB., Nam, JY., Cho, EJ., et al.[2023]

In a study of 36 patients with locally advanced non-small-cell lung cancer, the incidence of grade ≥2 radiation pneumonitis (RP) after concurrent chemoradiotherapy followed by durvalumab was 36%, indicating a notable risk of this side effect.

Higher dose-volume parameters of the lung were significantly associated with increased severity of RP, suggesting that careful monitoring of lung radiation exposure could help manage this risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and dose-volume relationship of radiation pneumonitis after concurrent chemoradiotherapy followed by durvalumab for locally advanced non-small cell lung cancer. Saito, S., Abe, T., Kobayashi, N., et al.[2022]

In a study involving 10 patients receiving palliative radiotherapy (RT) combined with durvalumab, the treatment was well tolerated, with only 50% experiencing mild to moderate adverse events, primarily G2 mucositis, and no severe adverse events reported.

The treatment showed promising efficacy, with a 60% objective response rate in evaluable lesions and a significant decrease in tumor growth rate after RT, indicating that durvalumab combined with RT may effectively reduce tumor size in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Levy, A., Massard, C., Soria, JC., et al.[2022]

Citations

1.

evidence.nejm.org

evidence.nejm.org/doi/full/10.1056/EVIDoa2200015

Durvalumab plus Gemcitabine and Cisplatin in Advanced ...

A phase 2 trial of durvalumab in combination with gemcitabine and cisplatin demonstrated promising efficacy, with an objective response rate of 72% and a ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10963573/

Durvalumab Plus Gemcitabine and Cisplatin in Patients ...

Durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer: an exploratory analysis of real-world data.

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0959804924008554

Durvalumab plus gemcitabine and cisplatin in advanced ...

The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC).

4.

academic.oup.com

academic.oup.com/oncolo/article/30/8/oyae306/7905746

Real-world effectiveness and prognostic factors of durvalumab ...

Our study showed comparable efficacy in an Asian population, with a median OS of 15.8 months and an ORR of 31.1% for durvalumab plus ...

5.

karger.com

karger.com/ocl/article/doi/10.1159/000541891/917478/Survival-Outcomes-of-Durvalumab-in-Combination

Survival Outcomes of Durvalumab in Combination with ...

Median OS was NR and median progression free survival (PFS) was 7.6 months, after a median follow-up of 13.5 months. The investigator-assessed ...

6.

evidence.nejm.org

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

Tremelimumab plus Durvalumab in Unresectable ...

Conclusions. STRIDE significantly improved overall survival versus sorafenib. Durvalumab monotherapy was noninferior to sorafenib for patients ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11632046/

Efficacy and safety of durvalumab rechallenge in advanced ...

This study provides the first, concrete evidence that durvalumab rechallenge is effective for HCC patients who are refractory to anti-PD-1 therapy.

8.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2023.41.4_suppl.TPS638

Durvalumab and tremelimumab for hepatocellular ...

This is a single-arm, open-label, Phase II, multicenter study designed to evaluate the safety and efficacy of durvalumab and tremelimumab for the treatment of ...

9.

ar.iiarjournals.org

ar.iiarjournals.org/content/44/9/3913

Change in Liver Function in Durvalumab Plus ...

This multicenter study aimed to examine the changes in liver function during DT treatment.

10.

touchoncology.com

touchoncology.com/gastrointestinal-cancers/journal-articles/long-term-survival-in-patients-with-advanced-hepatocellular-cancer-with-dual-immunotherapy-agents-tremelimumab-plus-durvalumab/

Long-term Survival in Patients with Advanced ...

The 4-year updated analysis confirmed substantial long-term survival benefits, with STRIDE showing a 25.2% 4-year OS rate compared with 15.1% ...