A Study of BBI608 Administrated With Sorafenib in Adult Patients With Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This is an open-label, multicenter, phase 1 study of BBI608 in combination with Sorafenib. This study population is adult Japanese patients with advanced hepatocellular carcinoma in Sorafenib combination therapy.

Official Title
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A Phase I Study of BBI608 Administrated With Sorafenib in Adult Patients With Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: BBI608
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or diagnosed imaging with hepatocellular carcinoma, and not indicated with a)-d) . Radiofrequency ablation therapy (RFA) Local therapy [such as percutaneous transhepatic ethanol injection therapy (PEIT), Microwave coagulation therapy (MCT)] Transcatheter arterial embolization (TAE) Transcatheter arterial chemoembolization (TACE) ≥ 20 years of age. Not treatment with systemic chemotherapy. Signed written informed consent must be obtained and documented. Life expectancy ≥ 3 months. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Must be Child Pugh Class A. Hemoglobin ≥ 8.5 mg/dl. Absolute neutrophil count ≥ 1.5 x 10^9 /L. Platelets ≥ 75 x 10^9/L. Creatinine ≤ 1.5 x ULN. Total Bilirubin ≤ 3.0 mg/dl. Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) ≤ 5.0 x the upper limit of normal (ULN). Females of childbearing potential must have a negative serum pregnancy test. Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose. Exclusion Criteria: Have had any t a)-i) treatment less than 28 days prior to beginning the enrolment. Radiation therapy Hormone therapy Immune therapy Hyperthermia Surgical procedure Local therapy (such as RFA, PEIT, MCT) TAE TACE other anti- tumour treatment Have had a brain metastases with a symptom or requiring treatment. Have had coinstantaneous active multiple cancers. Have had a carcinomatous pleural effusion, ascites, or cardiac effusion requiring treatment. Esophageal varix requiring treatment. Patient of pregnancy or possibility of pregnancy, and planning breastfeeding by the end of BBI608 administration after 30days. Crohns disease, ulcerative colitis, or historical surgery of extensively small intestine resection. Unable or unwilling to swallow BBI608 capsules or Sorafenib tablets. Uncontrolled inter-current illness (such as Grade 3active infection, or serious respiratory disease). HIV infection. Abnormal ECGs which are clinically significant within 28 days before enrolment. Patients who are New York Heart Association (NYHA) functional classes III, or IV, or unstable angina. Patients newly expressing angina within three months before the enrolment. Have had myocardial infarction within six months before the enrolment. Administrating with antiarrhythmic drug. Have received other investigational products or post-marketing investigational products within 4 weeks of the first dose of BBI608. Prior treatment with BBI608. Hypersensitivity to Sorafenib or any other component of Sorafenib. Ineligible for participation in the study in the opinion of the Investigators.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BBI608 puls Sorafenib<br> | Drug: BBI608<br>* Administered continuously twice daily with doses separated by 9-15 hours.<br>Drug: Sorafenib<br>* Sorafenib 400 mg twice daily (800 mg total daily dose).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety and tolerability of BBI608 given in combination with Sorafenib by reporting of adverse events and serious adverse events. |  | 7 month | 
| Assessment of dose-limiting toxicities (DLTs). |  | 29 days | 
| Pharmacokinetic profile of BBI608 when administered in combination with Sorafenib. |  | On day 1: Prior to BBI608 dosing and 2,4,6,8,10,12 and 24 hours after the first dose. On day 29: Prior to BBI608 dosing and 2,4,6,8,10,12 and 24 hours after the first dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the preliminary anti-tumour activity. | Anti-tumour activity is assessed every 8 weeks from the first dose of BBI608 after the last dose of BBI608.The radiologic assessments will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST for patients with hepatocellular carcinoma. | Approximately 7 months | 
| Progression Free Survival | The time the participant stays on study until progression will be measured and recorded. | Approximately 7 month | 
| Overall Survival | Participants follow-up for overall survival will occur. Maximum follow-up time is 1 year after the initial administration of the last subject. | Approximately 1 year |