21 Participants Needed

Radiotherapy + Immunotherapy for Liver Cancer

KB
HC
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Overseen ByJamese Johnson
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Mary Feng, MD
Must be taking: Antivirals
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well standard of care hypofractionated radiation therapy followed by durvalumab with or without tremelimumab works in treating patients with hepatocellular cancer (liver cancer) that has spread to other places in the body (advanced) and that is growing, spreading, or getting worse (progressing) after treatment with PD-1 inhibitor immunotherapy. In some patients, cancer cells and immune cells start to express signals that stop the body's immune system from killing the cancer. New drugs being developed, such as durvalumab and tremelimumab, are designed to target and block these signals and may help increase the immune response to prevent or slow down cancer growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may help the immune system work even better. Giving durvalumab with or without tremelimumab after radiation therapy may work better than radiation therapy alone in treating patients with liver cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive medication, you must stop it at least 14 days before starting the trial, with some exceptions like certain steroids. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Durvalumab and Tremelimumab for liver cancer?

The combination of tremelimumab and durvalumab was approved by the FDA for treating unresectable hepatocellular carcinoma (a type of liver cancer) based on a study showing it improved overall survival compared to another drug, sorafenib. Patients lived a median of 16.4 months with this combination, compared to 13.8 months with sorafenib.12345

Is the combination of durvalumab and tremelimumab safe for humans?

The combination of durvalumab and tremelimumab has been studied for safety in various cancers, including liver cancer. Common side effects include rash, fatigue, diarrhea, itching, muscle pain, and abdominal pain. Serious side effects occurred in about 32.6% of patients, which is higher compared to durvalumab alone.13678

How is the treatment of radiotherapy combined with durvalumab and tremelimumab unique for liver cancer?

This treatment is unique because it combines radiotherapy with two immunotherapy drugs, durvalumab and tremelimumab, which work together to enhance the body's immune response against liver cancer. This combination aims to improve outcomes by using the body's own immune system to fight the cancer, which is different from traditional treatments that may rely solely on surgery or chemotherapy.3591011

Research Team

MF

Mary Feng, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults with advanced liver cancer that has worsened after PD-1 inhibitor therapy. They must have manageable hepatitis B, good organ function, no history of certain autoimmune diseases or immunodeficiencies, and not be on conflicting medications or treatments. Participants need to agree to use contraception and have a life expectancy of at least 12 weeks.

Inclusion Criteria

I am on antiviral therapy for hepatitis B with low viral load.
I am over 18, expected to live more than 12 weeks, and weigh more than 30 kg.
My liver is functioning well enough, meeting specific health criteria.
See 9 more

Exclusion Criteria

I haven't had major surgery or cancer treatment recently and have no ongoing side effects.
I have previously been treated with CTLA-4 or PD-L1 inhibitors, or have had an organ transplant.
I've had radiation that now makes further treatment unsafe.
See 4 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo standard of care hypofractionated radiation therapy over 5 fractions once daily for 5 days

1 week
5 visits (in-person)

Treatment

Patients receive durvalumab with or without tremelimumab intravenously. Treatment repeats every 28 days for up to 2 years

Up to 24 months
1 visit every 28 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 2 months
1 visit every 2 months (in-person)

Treatment Details

Interventions

  • Durvalumab
  • Hypofractionated Radiation Therapy
  • Tremelimumab
Trial OverviewThe study tests if hypofractionated radiation followed by durvalumab alone or with tremelimumab improves outcomes in liver cancer patients who've progressed on PD-1 inhibitors. It's seeing whether these drugs can boost the immune system's response against cancer when given after targeted high-dose radiation therapy.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm II (hypofractionated RT, durvalumab, tremelimumab)Experimental Treatment3 Interventions
Patients undergo standard of care hypofractionated RT over 5 fractions QD for 5 days in the absence of disease progression or unacceptable toxicity. Within 3-10 days after completion of RT, patients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1. Treatment with durvalumab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who complete the first dose of tremelimumab and demonstrate clinical benefit based upon radiographic tumor regression and/or other clinical response without progression for at least 6 cycles or 6 months on treatment, whichever is shorter, and subsequently have evidence of progressive disease during the durvalumab monotherapy portion may receive a repeat dose of tremelimumab at the next scheduled cycle of treatment with durvalumab per physician discretion.
Group II: Arm I (hypofractionated RT, durvalumab)Experimental Treatment2 Interventions
Patients undergo standard of care hypofractionated RT over 5 fractions QD for 5 days in the absence of disease progression or unacceptable toxicity. Within 3-10 days after completion of RT, patients receive durvalumab IV over 1 hour on day 1. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

🇪🇺
Approved in European Union as Imfinzi for:
  • Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸
Approved in United States as Imfinzi for:
  • Extensive-stage small cell lung cancer (ES-SCLC)
  • Limited-stage small cell lung cancer (LS-SCLC)
  • Locally advanced or metastatic urothelial carcinoma
🇯🇵
Approved in Japan as Imfinzi for:
  • Not specified in provided sources

Find a Clinic Near You

Who Is Running the Clinical Trial?

Mary Feng, MD

Lead Sponsor

Trials
1
Recruited
20+

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

Findings from Research

The FDA approved tremelimumab in combination with durvalumab for treating unresectable hepatocellular carcinoma based on the HIMALAYA study, which showed a significant improvement in overall survival (OS) compared to sorafenib, with a median OS of 16.4 months versus 13.8 months.
Common adverse reactions in patients receiving the combination treatment included rash, fatigue, diarrhea, and abdominal pain, occurring in 20% or more of patients, indicating the need for monitoring during treatment.
FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma.Patel, TH., Brewer, JR., Fan, J., et al.[2023]
In the phase 3 MYSTIC study involving 488 treatment-naïve patients with metastatic non-small-cell lung cancer, durvalumab alone or in combination with tremelimumab showed significant improvements in patient-reported outcomes (PROs) compared to chemotherapy, particularly in reducing fatigue and appetite loss.
Patients receiving durvalumab-containing treatments experienced a longer time to deterioration in quality of life and physical functioning, indicating that these treatments may help maintain better overall well-being without negatively impacting quality of life.
Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC).Garon, EB., Cho, BC., Reinmuth, N., et al.[2022]
The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.
This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.
DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy.Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

References

FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma. [2023]
Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). [2022]
DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]
Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). [2023]
Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. [2023]
Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]
Tremelimumab: First Approval. [2023]
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]
A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma. [2023]
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]
Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited). [2023]