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Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma (HIMALAYA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03298451
Recruitment Status : Recruiting
First Posted : October 2, 2017
Last Update Posted : July 8, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Durvalumab Drug: Tremelimumab (Regimen 1) Drug: Tremelimumab (Regimen 2) Drug: Sorafenib Drug: Durvalumab (Regimen 1) Drug: Durvalumab (Regimen 2) Phase 3

Detailed Description:

The study population includes patients 18 years of age or older with advanced HCC, Barcelona Clinic Liver Cancer stage B not eligible for locoregional therapy or stage C, and Child-Pugh A classification liver disease. Patients must not have received any prior systemic therapy for unresectable HCC.

Patients in all treatment arms may continue receiving their originally assigned treatment, at the Investigator's discretion, until progression

Patients in all arms with confirmed PD who, in the Investigator's opinion, continue to receive benefit from their assigned treatment and meet the criteria for treatment in the setting of PD may continue to receive their assigned treatment.

If a patient discontinues study drug(s) due to disease progression, the patient will enter survival follow-up. Patients who have discontinued treatment due to toxicity or symptomatic deterioration or who have commenced subsequent anticancer therapy, will have tumor assessments until confirmed PD and will be followed for survival.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1504 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
Actual Study Start Date : October 11, 2017
Actual Primary Completion Date : August 27, 2021
Estimated Study Completion Date : August 27, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1
Durvalumab
 Drug: Durvalumab
Durvalumab IV (intravenous infusion).
Other Name: MEDI4736
Experimental: Arm 2
Durvalumab in combination with tremelimumab (Regimen 1)
 Drug: Tremelimumab (Regimen 1)
Tremelimumab IV (intravenous infusion).

Drug: Durvalumab (Regimen 1)
Durvalumab IV (intravenous infusion).
Experimental: Arm 3
Durvalumab in combination with tremelimumab (Regimen 2)
 Drug: Tremelimumab (Regimen 2)
Tremelimumab IV (intravenous infusion).

Drug: Durvalumab (Regimen 2)
Durvalumab IV (intravenous infusion).
Active Comparator: Arm 4
Sorafenib
 Drug: Sorafenib
Sorafenib, as per standard of care


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From the date of randomization until death due to any cause, assessed up to 4 years. ]

Secondary Outcome Measures :
  1. Time to Progression (TTP) [ Time Frame: From randomization until objective tumor progression, assessed up to 4 years. ]
  2. Progression-free survival (PFS) [ Time Frame: From date of randomization until the date of objective disease progression or death, assessed up to 4 years. ]
  3. Objective response rate (ORR) [ Time Frame: Until progression, assessed up to 4 years. ]
  4. Disease control rate (DCR) [ Time Frame: Until progression, assessed up to 4 years. ]
  5. Duration of response (DoR) [ Time Frame: From the date of first documented response (RECIST 1.1.) until the first date of documented progression or death in the absence of disease progression, assessed up to 4 years. ]

Other Outcome Measures:
  1. Adverse events [ Time Frame: From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 4 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  • HCC based on histopathological confirmation
  • No prior systemic therapy for HCC
  • Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C
  • Child-Pugh Score class A
  • ECOG performance status of 0 or 1 at enrollment

Exclusion criteria

  • Hepatic encephalopathy within past 12 months or requirement for medication to prevent or control encephalopathy
  • Clinically meaningful ascites
  • Main portal vein tumor thrombosis
  • Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
  • HBV and HVC co-infection, or HBV and Hep D co-infection
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298451


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03298451    
Other Study ID Numbers: D419CC00002
First Posted: October 2, 2017    Key Record Dates
Last Update Posted: July 8, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Hepatocellular Carcinoma Non-Resectable
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
 Sorafenib
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs