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

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03298451
Collaborator
(none)
1,504
Enrollment
175
Locations
4
Arms
82.5
Anticipated Duration (Months)
8.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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
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

Study Type:
Interventional
Anticipated 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 :
Oct 11, 2017
Actual Primary Completion Date :
Aug 27, 2021
Anticipated Study Completion Date :
Aug 27, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1

Durvalumab

Drug: Durvalumab
Durvalumab IV (intravenous infusion).
Other Names:
  • 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

    Primary Outcome Measures

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

    Secondary Outcome Measures

    1. Time to Progression (TTP) [From randomization until objective tumor progression, assessed up to 4 years.]

    2. Progression-free survival (PFS) [From date of randomization until the date of objective disease progression or death, assessed up to 4 years.]

    3. Objective response rate (ORR) [Until progression, assessed up to 4 years.]

    4. Disease control rate (DCR) [Until progression, assessed up to 4 years.]

    5. Duration of response (DoR) [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 [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

    Criteria

    Ages Eligible for Study:
    18 Years to 100 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Locations

    Site City State Country Postal Code
    1 Research Site Los Angeles California United States 90048
    2 Research Site Orange California United States 92868
    3 Research Site San Francisco California United States 94158
    4 Research Site Washington District of Columbia United States 20007
    5 Research Site Fort Myers Florida United States 33916
    6 Research Site Jacksonville Florida United States 32224
    7 Research Site Westwood Kansas United States 66205
    8 Research Site Baltimore Maryland United States 21231
    9 Research Site Ann Arbor Michigan United States 48109
    10 Research Site Rochester Minnesota United States 55905
    11 Research Site New York New York United States 10065
    12 Research Site Charlotte North Carolina United States 28262
    13 Research Site Portland Oregon United States 97213
    14 Research Site Pittsburgh Pennsylvania United States 15237
    15 Research Site Dallas Texas United States 74235
    16 Research Site Dallas Texas United States 75216
    17 Research Site Dallas Texas United States 75235
    18 Research Site Houston Texas United States 77030
    19 Research Site Houston Texas United States 77090
    20 Research Site Murray Utah United States 84107
    21 Research Site Barretos Brazil
    22 Research Site Curitiba Brazil
    23 Research Site Florianopolis Brazil
    24 Research Site Porto Alegre Brazil
    25 Research Site Rio de Janeiro Brazil
    26 Research Site Sao Paulo Brazil
    27 Research Site Sao Paulo Brazil
    28 Research Site Calgary Alberta Canada T2N 4N2
    29 Research Site Edmonton Alberta Canada T6G 1Z2
    30 Research Site Hamilton Ontario Canada L8V 5C2
    31 Research Site Kingston Ontario Canada K7L 2V7
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    33 Research Site Toronto Ontario Canada M4N 3M5
    34 Research Site Montreal Quebec Canada H2X 0A9
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    37 Research Site Beijing China
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    129 Research Site Ilsan Gyeonggi-do Korea, Republic of 10408
    130 Research Site Seongnam-si Gyeonggi-do Korea, Republic of 13620
    131 Research Site Busan Korea, Republic of 49241
    132 Research Site Daegu Korea, Republic of 41944
    133 Research Site Seoul Korea, Republic of 03080
    134 Research Site Seoul Korea, Republic of 03722
    135 Research Site Seoul Korea, Republic of 05505
    136 Research Site Seoul Korea, Republic of 06351
    137 Research Site Moscow Russian Federation
    138 Research Site Moscow Russian Federation
    139 Research Site Murmansk Russian Federation
    140 Research Site Nizhniy Novgorod Russian Federation
    141 Research Site Novosibirsk Russian Federation
    142 Research Site Obninsk Russian Federation
    143 Research Site Omsk Russian Federation
    144 Research Site Saint Petersburg Russian Federation
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    146 Research Site Saint Petersburg Russian Federation
    147 Research Site Ufa Russian Federation
    148 Research Site Barcelona Spain
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    153 Research Site Chiayi Taiwan
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    160 Research Site Bangkok Thailand
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    166 Research Site Dnipro Ukraine
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    173 Research Site Uzhgorod Ukraine
    174 Research Site Hanoi Vietnam
    175 Research Site Hochiminh Vietnam

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT03298451
    Other Study ID Numbers:
    • D419CC00002
    First Posted:
    Oct 2, 2017
    Last Update Posted:
    Jul 8, 2022
    Last Verified:
    Jul 1, 2022
    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
    Sorafenib
    Durvalumab
    Tremelimumab
    Antibodies, Monoclonal

    Study Results

    No Results Posted as of Jul 8, 2022