Clinical trial NCT01101906: A Randomized, Placebo-controlled, Double-blind Phase 2 Study With OSI-906 in Patients With Advanced HCC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced Hepatocellular Carcinoma (HCC)
Keywords: HCC
OSI-906
Hepatocellular Carcinoma
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2010-04-12
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Time to progression (TTP)
timeFrame: 20 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 23 months
measure: Progression Free Survival (PFS)
timeFrame: 23 months
measure: Time to Progression (including clinical progression) (TTPc)
timeFrame: 23 months
measure: Disease Control Rate (DCR)
timeFrame: 23 months
measure: Overall Response Rate
timeFrame: 23 months
measure: Time to progression in patients with hepatitis B virus (HBV) and/or hepatitis C virus (HVC)
timeFrame: 23 months
measure: Progression Free Survival in patients with HBV and/or HCV
timeFrame: 23 months
measure: Overall Survival in patients with HBV and/or HCV
timeFrame: 23 months
measure: Overall Response Rate in patients with HBV and/or HCV
timeFrame: 23 months
measure: Safety assessed via physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECGs) and recording adverse events
timeFrame: 23 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: New Orleans
country: United States
facility: Tulane University Health Services Center
state: Louisiana
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Brussells
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Bondy Cedex
country: France
facility: Hopital Jean Verdier - Dervice d'Hepato-Gastroenterologie
city: Creteil cedex
country: France
facility: Hôpital Henri Mondor
city: Marseille Cedex 5
country: France
facility: Hopital de la Timone
city: Nice cedex 03
country: France
facility: Hopital l'Archet 2
city: Paris cedex 12
country: France
facility: Hôpital Saint-Antoine
city: Paris cedex 12
country: France
facility: Hôpital de Tenon
city: Saint Herblain cedex
country: France
facility: Centre Rene Gauducheau
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Homburg
country: Germany
facility: Universitatsklinikum des Saarlandes
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg A.ö.R.
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Milano
country: Italy
facility: Fondazione Ca' Granda Ospedale Maggiore Policlinico, Divisione di Gastroenterologia I
city: Napoli
country: Italy
facility: Ospedale Fatebenefratelli, Dipartimento Medicina Interna
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale per lo studio e la cura dei tumori Fondazione G. Pascale-SSD Epatobiliare
city: Palermo
country: Italy
facility: Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ISMETT-Dipartimento di Epatologia e Gastroenterologia
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Centre
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago de Compostela
state: Coruna
city: Barcelona
country: Spain
facility: Hospital Clinic Provincial
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: TaoYuan
country: Taiwan
facility: Chang Gung Medical Foundation LinKou Branch
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: