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

Advanced Hepatocellular Carcinoma (HCC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01101906
• Other study ID #: OSI-906-206
• Secondary ID: 2010-018739-17
• Status: Terminated
• Phase: Phase 2
• Start date: January 10, 2011
• Est. completion date: December 28, 2011

Study information

• Verified date: August 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: December 28, 2011
• Est. primary completion date: November 4, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma (HCC)
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• OSI-906
OSI-906 administered orally
• Placebo
Matching placebo administered orally

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussells
Belgium	Universitair Ziekenhuis Gent	Gent
France	Hopital Jean Verdier - Dervice d'Hepato-Gastroenterologie	Bondy Cedex
France	Hôpital Henri Mondor	Creteil cedex
France	Hopital de la Timone	Marseille Cedex 5
France	Hopital l'Archet 2	Nice cedex 03
France	Hôpital de Tenon	Paris cedex 12
France	Hôpital Saint-Antoine	Paris cedex 12
France	Centre Rene Gauducheau	Saint Herblain cedex
Germany	Universitatsklinikum Essen	Essen
Germany	Universitätsklinikum Halle	Halle
Germany	Universitatsklinikum des Saarlandes	Homburg
Germany	Universitätsklinikum Magdeburg A.ö.R.	Magdeburg
Hong Kong	Queen Mary Hospital	Hong Kong
Italy	Fondazione Ca' Granda Ospedale Maggiore Policlinico, Divisione di Gastroenterologia I	Milano
Italy	IRCCS Istituto Nazionale per lo studio e la cura dei tumori Fondazione G. Pascale-SSD Epatobiliare	Napoli
Italy	Ospedale Fatebenefratelli, Dipartimento Medicina Interna	Napoli
Italy	Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ISMETT-Dipartimento di Epatologia e Gastroenterologia	Palermo
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Singapore	Johns Hopkins Singapore International Medical Centre	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Clinic Provincial	Barcelona
Spain	Hospital Puerta de Hierro Majadahonda	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Santiago de Compostela	Santiago de Compostela	Coruna
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chang Gung Medical Foundation LinKou Branch	TaoYuan
United States	University of California - Los Angeles	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tulane University Health Services Center	New Orleans	Louisiana
United States	Oregon Health & Science University	Portland	Oregon
United States	Seattle Cancer Care Alliance University of Washington	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	Date of randomization until the documented date of death	23 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Response Rate	Proportion of patients with a best overall response of CR or PR based on RECIST version 1.1 criteria	23 months
Secondary	Time to progression in patients with hepatitis B virus (HBV) and/or hepatitis C virus (HVC)		23 months
Secondary	Progression Free Survival in patients with HBV and/or HCV		23 months
Secondary	Overall Survival in patients with HBV and/or HCV		23 months
Secondary	Overall Response Rate in patients with HBV and/or HCV		23 months
Secondary	Safety assessed via physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECGs) and recording adverse events		23 months

External Links

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