A Randomized, Placebo-controlled, Double-blind Phase 2 Study With OSI-906 in Patients With Advanced HCC

A Randomized, Placebo-controlled, Double-blinded Phase 2 Study of Second-line Treatment With OSI-906 in Patients With Advanced Hepatocellular Carcinoma (HCC) After Failure of First-line Treatment With Sorafenib

This is a randomized, placebo-controlled, double-blind phase 2 study of OSI-906 or placebo at a continuous 150 mg twice daily (BID) dose.

Study Overview

• Status: Terminated
• Conditions: Advanced Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: OSI-906; Drug: Placebo

Detailed Description

Adult patients with advanced HCC previously treated with sorafenib will be randomized 2:1 to receive either single agent OSI-906 or placebo

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussells, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• France
  • Bondy Cedex, France, 93143
    • Hopital Jean Verdier - Dervice d'Hepato-Gastroenterologie
  • Creteil cedex, France, 94010
    • Hôpital Henri Mondor
  • Marseille Cedex 5, France, 13385
    • Hopital de la Timone
  • Nice cedex 03, France, 6202
    • Hopital l'Archet 2
  • Paris cedex 12, France, 75012
    • Hopital Saint-Antoine
  • Paris cedex 12, France, 75020
    • Hôpital de Tenon
  • Saint Herblain cedex, France, 44805
    • Centre Rene Gauducheau
• Germany
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Halle, Germany, 06097
    • Universitätsklinikum Halle
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg A.ö.R.
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• Italy
  • Milano, Italy, 20122
    • Fondazione Ca' Granda Ospedale Maggiore Policlinico, Divisione di Gastroenterologia I
  • Napoli, Italy, 80123
    • Ospedale Fatebenefratelli, Dipartimento Medicina Interna
  • Napoli, Italy, 80131
    • IRCCS Istituto Nazionale per lo studio e la cura dei tumori Fondazione G. Pascale-SSD Epatobiliare
  • Palermo, Italy, 90127
    • Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ISMETT-Dipartimento di Epatologia e Gastroenterologia
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Pusan National University Hospital
  • Daegu, Korea, Republic of, 700-721
    • Kyungpook National University Hospital
  • Goyang-si, Korea, Republic of, 410-769
    • National Cancer Center
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital
  • Seoul, Korea, Republic of, 110-774
    • Seoul National University Hospital
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
  • Singapore, Singapore, 308433
    • Johns Hopkins Singapore International Medical Centre
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Provincial
  • Madrid, Spain, 28220
    • Hospital Puerta de Hierro Majadahonda
  • Pamplona, Spain, 31008
    • Clinica Universitaria de Navarra
  • Coruna
    • Santiago de Compostela, Coruna, Spain, 15706
      • Hospital Clinico Universitario de Santiago de Compostela
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • TaoYuan, Taiwan, 333
    • Chang Gung Medical Foundation Linkou Branch
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California - Los Angeles
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Services Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 52336
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of advanced HCC. Clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients is acceptable. For patients without cirrhosis histological confirmation is mandatory
• Patients must have received prior systemic treatment for advanced HCC with sorafenib and had confirmed disease progression or had discontinued sorafenib due to a drug related toxicity
• Patient has received their last dose of sorafenib at least 14 days prior to randomization
• Patient has recovered from sorafenib or investigational agent related toxicity to ≤ grade 2
• Measurable disease according to RECIST (version 1.1)
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 - 1
• Child-Pugh Status A or B(7)
• Barcelona Clinic Liver Cancer (BCLC) stage B/C
• Previous local therapy (eg, surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) is permitted if ≥ 21 days before randomization
• Fasting glucose ≤ 150 mg/dL (8.3 mmol/L). Concurrent use of non-insulinotropic oral antihyperglycemic therapy is permitted if the dose has been stable for ≥ 4 weeks at the time of randomization

• Following laboratory parameters (determined by laboratory):

  • Platelets ≥ 60 x 10^9/L
  • Hemoglobin ≥ 8.5 g/dL
  • Absolute neutraphil count (ANC) ≥ 1.5 x 10^9/L
  • Potassium within normal limits (supplementation may be used)
  • Partial thrombopastin time (PTT) ≤ 2.3 x Upper Limit of Normal (ULN)
  • Magnesium within normal limits (supplementation may be used)
  • Calcium within normal limits (supplementation may be used)

• Adequate organ function (for a HCC population):

  • Liver function test (LFT) ≤ 5 x ULN
  • Albumin ≥ 2.8 g/dL
  • Total bilirubin ≤ 2.8 mg/dL
  • Creatinine ≤ 1.5 x ULN
  • International normalized ratio (INR) ≤ 2.3
• Estimated life expectancy ≥ 12 weeks based on an investigator assessment of recent changes in laboratory values, performance status, and other clinical criteria
• Patients, both males and females, with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must agree to practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to randomization
• Patients must provide written informed consent to participate in the study
• Prior radiation therapy is permitted provided patients have recovered from the acute, toxic effects of radiotherapy prior to randomization. A minimum of 21 days must have elapsed between the end of radiotherapy and randomization; and
• Prior surgery is permitted provided that the surgery was done ≤ 28 days prior to randomization and adequate wound healing has occurred prior to randomization

Exclusion Criteria:

• Child-Pugh B (8 - 9) or C
• Patients who are candidates for potentially curative intervention (ie, surgical resection or transplantation)
• Type 1 diabetes mellitus or Type 2 diabetes mellitus currently requiring insulinotropic or insulin therapy
• Prior insulin-like growth factor - 1 receptor (IGF-1R) therapy
• Patients requiring interferon
• Patients with uncontrolled symptomatic ascites
• Prior investigational agent within 21 days prior to randomization
• History of poorly controlled gastrointestinal disorders that could affect the absorption of study drug (eg, Crohn's disease, ulcerative colitis, etc)
• History of organ allograft including liver transplant

• Malignancy other than HCC within the past 3 years:

  • Exceptions: resected basal cell or squamous cell carcinoma of the skin, cured in situ cervical carcinoma, cured ductal carcinoma in situ of the breast, and/or cured superficial bladder cancer
• History (within last 6 months) of significant cardiovascular disease unless the disease is well-controlled. Significant cardiac disease includes second/third degree heart block; clinically significant ischemic heart disease; superior vena cava (SVC) syndrome; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea)
• History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (≥ grade 3), left bundle branch block (LBBB), or asymptomatic sustained ventricular tachycardia are not allowed. Patients with atrial fibrillation controlled by medication are not excluded
• QTcF interval at screening ≥ 450 msec
• Use of drugs that have a known risk of causing Torsades de Pointes (TdP) ('Torsades List' on www.azcert.org/medical-pros/drug-lists/by category.cfm)are prohibited within 14 days prior to randomization
• Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded
• History of cerebrovascular accident (CVA) within 6 months prior to randomization or that resulted in ongoing neurologic instability
• Active infection or serious underlying medical condition (including any type of active seizure disorder within 12 months prior to randomization) that would impair the ability of the patient to receive study drug
• History of human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS)-related illness or serious acute or chronic illness
• History of any psychiatric or neurologic condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
• Pregnant or breast-feeding females
• Symptomatic brain metastases that are not stable, require steroids, are potentially life threatening, or that have required radiation within 28 days prior to randomization; and/or
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: OSI-906; 150 mg BID	Drug: OSI-906; OSI-906 administered orally
Placebo Comparator: Arm B: Placebo; Placebo BID	Drug: Placebo; Matching placebo administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression (TTP)	Time from randomization to radiological disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	20 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Date of randomization until the documented date of death	23 months
Progression Free Survival (PFS)	Time from randomization to radiological disease progression based on RECIST version 1.1 assessed by investigator or death due to any cause whichever occurs first	23 months
Time to Progression (including clinical progression) (TTPc)	Time from randomization to progression (either radiological disease progression based on RECIST version 1.1 or symptomatic clinical progression as assessed by investigator)	23 months
Disease Control Rate (DCR)	Proportion of patients with a best overall response of complete response (CR), partial response (PR), or stable disease based on RECIST version 1.1 criteria	23 months
Overall Response Rate	Proportion of patients with a best overall response of CR or PR based on RECIST version 1.1 criteria	23 months
Time to progression in patients with hepatitis B virus (HBV) and/or hepatitis C virus (HVC)		23 months
Progression Free Survival in patients with HBV and/or HCV		23 months
Overall Survival in patients with HBV and/or HCV		23 months
Overall Response Rate in patients with HBV and/or HCV		23 months
Safety assessed via physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECGs) and recording adverse events		23 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2011
• Primary Completion (Actual): November 4, 2011
• Study Completion (Actual): December 28, 2011

Study Registration Dates

• First Submitted: April 8, 2010
• First Submitted That Met QC Criteria: April 8, 2010
• First Posted (Estimate): April 12, 2010

Study Record Updates

• Last Update Posted (Actual): September 5, 2018
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; HCC; OSI-906
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: OSI-906-206; 2010-018739-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."