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

This study has been terminated.
(Company decided not to pursue the development of this drug in this patient population at this time)
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01101906
First received: April 8, 2010
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Advanced Hepatocellular Carcinoma (HCC)
Drug: OSI-906
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Time to progression (TTP) [ Time Frame: 20 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 23 months ] [ Designated as safety issue: No ]
    Date of randomization until the documented date of death

  • Progression Free Survival (PFS) [ Time Frame: 23 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 23 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 23 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 23 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 23 months ] [ Designated as safety issue: No ]
  • Progression Free Survival in patients with HBV and/or HCV [ Time Frame: 23 months ] [ Designated as safety issue: No ]
  • Overall Survival in patients with HBV and/or HCV [ Time Frame: 23 months ] [ Designated as safety issue: No ]
  • Overall Response Rate in patients with HBV and/or HCV [ Time Frame: 23 months ] [ Designated as safety issue: No ]
  • Safety assessed via physical examination, vital signs, clinical laboratory tests, electrocardiograms (ECGs) and recording adverse events [ Time Frame: 23 months ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: October 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01101906

  Show 41 Study Locations
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01101906     History of Changes
Other Study ID Numbers: OSI-906-206, 2010-018739-17
Study First Received: April 8, 2010
Last Updated: December 10, 2012
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Germany: Federal Institute for Drugs and Medical Devices
Spain: Ministry of Health and Consumption
Hong Kong: Department of Health
Taiwan: Department of Health
South Korea: Korea Food and Drug Administration (KFDA)
Singapore: Health Sciences Authority

Keywords provided by Astellas Pharma Inc:
OSI-906
HCC
Hepatocellular Carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 28, 2014