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

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ClinicalTrials.gov Identifier: NCT03298451
Recruitment Status : Recruiting
First Posted : October 2, 2017
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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 unresectable 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 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 Unresectable Hepatocellular Carcinoma
Actual Study Start Date : October 11, 2017
Estimated Primary Completion Date : March 27, 2020
Estimated Study Completion Date : March 26, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

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




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. ]
  6. Health status/quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30) [ Time Frame: From randomization up to approximately 3 months from the treatment discontinuation, assessed up to 4 years. ]
  7. Presence of ADA for durvalumab and tremelimumab [ Time Frame: Starting prior to the first dose of the treatment up to approximately 3 months from the treatment discontinuation, assessed up to 4 years. ]
  8. The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by trough concentration [ Time Frame: Starting prior to the first dose of the treatment up to approximately 3 months from the treatment discontinuation, assessed up to 4 years. ]
  9. Disease-related symptoms measured by EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) [ Time Frame: From randomization up to approximately 3 months from the treatment discontinuation, assessed up to 4 years. ]
  10. The pharmacokinetics (PK) of durvalumab and tremelimumab as determined by peak concentration [ Time Frame: Starting prior to the first dose of the treatment up to approximately 3 months from the treatment discontinuation, 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 ]


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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 (unresectable hepatocellular carcinoma) histopathological diagnosis confirmation based on tumor tissue
  • 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
  • Ascites that your doctor will manage by increasing your medications or by performing non-invasive methods (eg, paracentesis) to control, within 6 months prior to the first scheduled dose.
  • 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

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

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Sponsors and Collaborators
AstraZeneca

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03298451     History of Changes
Other Study ID Numbers: D419CC00002
First Posted: October 2, 2017    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018

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:
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
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs