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

Trial Summary

What is the purpose of this trial?

This study will compare outcomes for M1 iCCA patients treated with and without L-RT by reviewing iCCA patients found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT.

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.

What data supports the effectiveness of the treatment Cisplatin, Durvalumab, and Gemcitabine with radiation for liver cancer?

Research shows that combining durvalumab (an immune therapy) with radiation can be effective in treating certain lung cancers, and using gemcitabine and cisplatin (both chemotherapy drugs) with radiation has shown promise in treating pancreatic cancer. These findings suggest that similar combinations might be effective for liver cancer. ^{1 2 3 4 5}

Is the combination of systemic therapy and radiation generally safe for humans?

Durvalumab, a drug used in combination with radiation, has been studied in patients with lung cancer. In one study, 64.4% of patients experienced some side effects, with 21% having more severe reactions like lung inflammation, skin rash, and thyroid issues. This suggests that while the treatment can be safe, it may also cause significant side effects in some people. ^{6 7 8 9 10}

How is the treatment of Cisplatin, Durvalumab, and Gemcitabine with radiation unique for liver cancer?

This treatment is unique because it combines systemic therapy with radiation, using Cisplatin and Gemcitabine to enhance the effects of radiation, and Durvalumab, an immunotherapy drug, to potentially boost the body's immune response against liver cancer. This approach is different from standard treatments as it leverages the synergistic effects of chemotherapy, immunotherapy, and radiation. ^{1 11 12 13 14}

Research Team

Eugene Koay, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study. [2022]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Rationale and design of a phase II trial of durvalumab treatment in patients with NSCLC ineligible for stage III chemoradiotherapy following radiation monotherapy (SPIRAL-RT study). [2022]

4. United States 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of locally advanced pancreatic carcinoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Analysis of Durvalumab after Chemoradiation in Stage III Non-Small-Cell Lung Cancer. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A phase 2 trial of durvalumab treatment following radiation monotherapy in patients with non-small cell lung cancer ineligible for stage III chemoradiotherapy: The SPIRAL-RT study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A study of the efficacy and toxicity outcomes of extended durvalumab dosing in patients with stage III unresectable non-small cell lung cancer (NSCLC) during the COVID-19 pandemic. [2023]

9. United States 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. [2023]

10. Ireland 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. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Effect of chemoradiotherapy with gemcitabine and cisplatin on locoregional control in patients with primary inoperable pancreatic cancer. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study. [2022]