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A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT02519348
Recruitment Status : Recruiting
First Posted : August 10, 2015
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: Durvalumab + tremelimumab Biological: Durvalumab Biological: Tremelimumab Biological: Durvalumab + Bevacizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 545 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study of Safety, Tolerability, and Clinical Activity of Durvalumab and Tremelimumab Administered as Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Subjects With Advanced Hepatocellular Carcinoma
Actual Study Start Date : October 19, 2015
Estimated Primary Completion Date : October 30, 2020
Estimated Study Completion Date : October 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Durvalumab & Tremelimumab (Regimen 1)
Durvalumab in combination with Tremelimumab (Regimen 1)
Biological: Durvalumab + tremelimumab
Durvalumab will be administered by IV infusion in combination with tremelimumab.

Experimental: Durvalumab
Durvalumab given as monotherapy
Biological: Durvalumab
Durvalumab will be administered by IV infusion.

Experimental: Tremelimumab
Tremelimumab given as monotherapy
Biological: Tremelimumab
Tremelimumab will be administered by IV infusion.

Experimental: Durvalumab & Tremelimumab (Regimen 2)
Durvalumab in combination with Tremelimumab (Regimen 2)
Biological: Durvalumab + tremelimumab
Durvalumab will be administered by IV infusion in combination with tremelimumab.

Experimental: Durvalumab & Bevacizumab
Durvalumab in combination with Bevacizumab
Biological: Durvalumab + Bevacizumab
Durvalumab will be administered by IV infusion in combination with bevacizumab




Primary Outcome Measures :
  1. Number of subjects reporting adverse events and number of subjects reporting serious adverse events. [ Time Frame: Screening through 3 months after the last dose of study medication ]
  2. Number of subjects experiencing dose limiting toxicities [ Time Frame: First dose of study medications through 4 weeks after the first dose of study medication ]

Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Screening through 12 months after the last subject is randomized ]
  2. Duration of Response [ Time Frame: Screening through 12 months after the last subject is randomized ]
  3. Overall Survival [ Time Frame: Screening through 12 months after the last subject is randomized ]
  4. PD-L1 expression [ Time Frame: Screening through last dose of study medication ]
  5. Time to Progression [ Time Frame: From the date of first dosing to the first documentation of radiographic disease progression (per RECIST v1.1) ]
  6. Progression Free Survival [ Time Frame: Time from the date of first dosing to the first documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first ]
  7. Disease Control Rate [ Time Frame: Screening through 12 months after the last subject is randomized ]
  8. Time to Response [ Time Frame: Time from the first dose of investigational product to the first documentation of a subsequently confirmed objective response, assessed up to 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects
  2. 18 years and older (Japan-20 years and older)
  3. Confirmed HCC based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods.
  4. Immunotherapy-naïve
  5. Have either progressed on, are intolerant to, or refused treatment with sorafenib or another approved TKI. For arm 5 only: Have not received any prior systemic therapy for HCC.

Exclusion Criteria:

  1. Prior exposure to immune-mediated therapy
  2. Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
  3. GI Bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
  4. Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
  5. Main portal vein thrombosis (Vp4) as documented on imaging
  6. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment
  7. Active or prior documented autoimmune or inflammatory disease with some exceptions
  8. Current or prior use of immunosuppressive medication within 14 days with some exceptions

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): NCT02519348


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service 1-877-400-4656 AstraZeneca@emergingmed.com

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Sponsors and Collaborators
MedImmune LLC
Investigators
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Study Director: MedImmune, LLC MedImmune, LLC MedImmune LLC

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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02519348     History of Changes
Other Study ID Numbers: D4190C00022
First Posted: August 10, 2015    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: March 2019

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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 MedImmune LLC:
Hepatocellular Carcinoma
Immunotherapy
Antibodies, Monoclonal
Tremelimumab
MEDI4736
Durvalumab

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
Bevacizumab
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors