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Phase 3 Study of BGB-A317 Versus Sorafenib in Patients With Unresectable HCC

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ClinicalTrials.gov Identifier: NCT03412773
Recruitment Status : Recruiting
First Posted : January 26, 2018
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

Study Description
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Brief Summary:
This is a Phase 3, randomized, open-label, multicenter, global study designed to compare the efficacy and safety of BGB-A317 versus sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma. This study also includes a substudy investigating the safety, tolerability, PK, and preliminary efficacy in HCC in Japanese patients. In Japan, preliminary safety and tolerability will be evaluated (Safety Run-In Substudy) before Japanese patients are recruited in this Phase 3 study.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma (HCC) Drug: BGB-A317 Drug: Sorafenib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 660 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: RATIONALE-301: A Randomized, Open-label, Multicenter Phase 3 Study to Compare the Efficacy and Safety of BGB-A317 Versus Sorafenib as First-Line Treatment in Patients With Unresectable Hepatocellular Carcinoma
Actual Study Start Date : December 28, 2017
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : May 2022

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A: BGB-A317 & Safety Run-In Substudy [Japan Only] Drug: BGB-A317
BGB-A317: 200 mg once every 3 weeks (Q3W), intravenous dosing (IV)
Other Name: PD-1 ANTIBODY
Active Comparator: Arm B: Sorafenib Drug: Sorafenib
Sorafenib: 400 mg twice daily (BID), oral dosing
Other Name: Nexavar, BAY43-9006


Outcome Measures
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Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From date of randomization up to 4 years, approximately ]
  2. Safety Run-In Substudy[Japan only]: Percentage of patients with adverse events [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  3. Safety Run-In Substudy[Japan only]: Percentage of patients with dose-limiting toxicities (DLT) [Determination of the pivotal Phase 3 dose of BGB-A317 in Japanese patients] [ Time Frame: From the date of enrollment up to 28 days [DLT period]. ]
  4. Safety Run-In Substudy[Japan only]: Maximum Concentration (Cmax) of BGB-A317 [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  5. Safety Run-In Substudy[Japan only]: Trough Serum Concentration (Cmin) of BGB-A317 [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  6. Safety Run-In Substudy[Japan only]: Area Under the Curve (AUC) of BGB-A317 [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  7. Safety Run-In Substudy[Japan only]:Anti-Drug Antibodies (ADA) against BGB-A317 at Cmin [ Time Frame: From first dose of study treatment up to 4 years, approximately. ]
  8. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Vital Signs Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  9. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Physical Examination Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  10. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  11. Safety Run-In Substudy[Japan only]: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings [ Time Frame: From date of enrollment up to 4 years, approximately. ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately ]
  2. Progression-free survival (PFS) [ Time Frame: From date of randomization up to 4 years, approximately ]
  3. Duration of Response (DOR) [ Time Frame: From first determination of an objective response up to 4 years, approximately ]
  4. Time to Progression (TTP) [ Time Frame: From date of randomization up to 4 years, approximately. ]
  5. Health-Related Quality of Life (HRQoL) [ Time Frame: From date of enrollment up to 4 years, approximately. ]
  6. Disease Control Rate (DCR) [ Time Frame: From first dose of study treatment up to 4 years, approximately ]
  7. Clinical Benefit Rate (CBR) [ Time Frame: From first dose of study treatment up to 4 years, approximately ]
  8. Percentage of patients with adverse events [ Time Frame: From date of screening up to 4 years, approximately. ]
  9. Safety Run-In Substudy[Japan only]: Objective Response Rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately. ]
  10. Safety Run-In Substudy[Japan only]: Progression-free survival (PFS) [ Time Frame: From date of randomization up 4 years, approximately ]
  11. Safety Run-In Substudy[Japan only]: Duration of Response (DOR) [ Time Frame: From date of randomization up 4 years, approximately ]
  12. Safety Run-In Substudy[Japan only]: Overall Survival (OS) [ Time Frame: From date of randomization up 4 years, approximately ]
  13. Safety Run-In Substudy[Japan only]: Anti-BGB-A317 antibody [ Time Frame: From first dose of study treatment up 4 years, approximately ]
  14. Percentage of Participants With Clinically Significant Changes in Vital Signs Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
  15. Percentage of Participants With Clinically Significant Changes in Physical Examination Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
  16. Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Results Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]
  17. Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings [ Time Frame: From date of enrollment up to 4 years, approximately ]

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

Inclusion Criteria:

  • 1. Histologically confirmed diagnosis of HCC

    2. Barcelona Clinic Liver Cancer (BCLC) Stage B or C disease not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach

    3. No prior systemic therapy for HCC (with the exception of HCC patients enrolled in the safety run-in substudy [Japan only])

    4. Measurable disease

    5. Child-Pugh score A

    6. Easter Cooperative Oncology Group (ECOG) Performance Status ≤ 1

    7. Adequate organ function

Exclusion Criteria:

  • 1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology

    2. Tumor thrombus involving main trunk of portal vein or inferior vena cava

    3. Loco-regional therapy to the liver within 28 days before randomization

    4. Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization

    5. Bleeding or thrombotic disorder or any prescribed anticoagulant requiring therapeutic international normalized ratio monitoring (eg, warfarin or similar agents) at Screening, or within 6 months before randomization/enrollment

    6. Presence at Screening of active immune deficiency or autoimmune disease and/or prior history of any immune deficiency or autoimmune disease that may relapse

    7. Patient with any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before randomization

    8. History of interstitial lung disease or non-infectious pneumonitis, unless induced by radiation therapy

    9. QT interval corrected for heart rate (QTc) (corrected by Fridericia's method) > 450 msec at Screening

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): NCT03412773


Contacts
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Contact: Ginny Paton, Executive Director, Clinical Science 1 (877) 828-5568 clinicaltrials@beigene.com
Contact: Cindy Li, Medical Director 1 (877) 828-5568 clinicaltrials@beigene.com

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Sponsors and Collaborators
BeiGene
More Information
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03412773     History of Changes
Other Study ID Numbers: BGB-A317-301
2017-002423-19 ( EudraCT Number )
CTR20170882 ( Registry Identifier: Center for drug evaluation, CFDA )
First Posted: January 26, 2018    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: August 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 BeiGene:
Advanced liver cancer
RATIONALE-301

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
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action