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

Sponsor

Astellas Pharma Inc (Industry)

Overall Status

Terminated

CT.gov ID

NCT01101906

Collaborator

(none)

Enrollment

Locations

Arms

11.6

Actual Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma (HCC)	Drug: OSI-906 Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 10, 2011

Actual Primary Completion Date :

Nov 4, 2011

Actual Study Completion Date :

Dec 28, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Time to progression (TTP) [20 months]
Time from randomization to radiological disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary Outcome Measures

Overall Survival (OS) [23 months]
Date of randomization until the documented date of death
Progression Free Survival (PFS) [23 months]
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
Time to Progression (including clinical progression) (TTPc) [23 months]
Time from randomization to progression (either radiological disease progression based on RECIST version 1.1 or symptomatic clinical progression as assessed by investigator)
Disease Control Rate (DCR) [23 months]
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
Overall Response Rate [23 months]
Proportion of patients with a best overall response of CR or PR based on RECIST version 1.1 criteria
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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