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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03298451
Recruitment Status : Active, not recruiting
First Posted : October 2, 2017
Last Update Posted : November 1, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE September 19, 2017
First Posted Date  ICMJE October 2, 2017
Last Update Posted Date November 1, 2019
Actual Study Start Date  ICMJE October 11, 2017
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
Overall Survival (OS) [ Time Frame: From the date of randomization until death due to any cause, assessed up to 4 years. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03298451 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2019)
  • Time to Progression (TTP) [ Time Frame: From randomization until objective tumor progression, assessed up to 4 years. ]
  • Progression-free survival (PFS) [ Time Frame: From date of randomization until the date of objective disease progression or death, assessed up to 4 years. ]
  • Objective response rate (ORR) [ Time Frame: Until progression, assessed up to 4 years. ]
  • Disease control rate (DCR) [ Time Frame: Until progression, assessed up to 4 years. ]
  • 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. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • Time to Progression (TTP) [ Time Frame: From randomization until objective tumor progression, assessed up to 4 years. ]
  • Progression-free survival (PFS) [ Time Frame: From date of randomization until the date of objective disease progression or death, assessed up to 4 years. ]
  • Objective response rate (ORR) [ Time Frame: Until progression, assessed up to 4 years. ]
  • Disease control rate (DCR) [ Time Frame: Until progression, assessed up to 4 years. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
Current Other Pre-specified Outcome Measures
 (submitted: September 26, 2017)
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 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
Official Title  ICMJE A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab IV (intravenous infusion).
    Other Name: MEDI4736
  • Drug: Tremelimumab (Regimen 1)
    Tremelimumab IV (intravenous infusion).
  • Drug: Tremelimumab (Regimen 2)
    Tremelimumab IV (intravenous infusion).
  • Drug: Sorafenib
    Sorafenib, as per standard of care
  • Drug: Durvalumab (Regimen 1)
    Durvalumab IV (intravenous infusion).
  • Drug: Durvalumab (Regimen 2)
    Durvalumab IV (intravenous infusion).
Study Arms  ICMJE
  • Experimental: Arm 1
    Durvalumab
    Intervention: Drug: Durvalumab
  • Experimental: Arm 2
    Durvalumab in combination with tremelimumab (Regimen 1)
    Interventions:
    • Drug: Tremelimumab (Regimen 1)
    • Drug: Durvalumab (Regimen 1)
  • Experimental: Arm 3
    Durvalumab in combination with tremelimumab (Regimen 2)
    Interventions:
    • Drug: Tremelimumab (Regimen 2)
    • Drug: Durvalumab (Regimen 2)
  • Active Comparator: Arm 4
    Sorafenib
    Intervention: Drug: Sorafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2019)
1310
Original Estimated Enrollment  ICMJE
 (submitted: September 26, 2017)
1200
Estimated Study Completion Date  ICMJE October 30, 2020
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Canada,   China,   France,   Germany,   Hong Kong,   India,   Italy,   Japan,   Korea, Republic of,   Russian Federation,   Spain,   Taiwan,   Thailand,   Ukraine,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03298451
Other Study ID Numbers  ICMJE D419CC00002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP