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    Summary
    EudraCT Number:2012-003977-24
    Sponsor's Protocol Code Number:SGI-110-03
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-12-09
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2012-003977-24
    A.3Full title of the trial
    A Phase 2 Study of SGI-110 in the Treatment of Advanced Hepatocellular Carcinoma (HCC) Subjects Who Failed Prior Treatment with Sorafenib
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of SGI-110 in people with advanced hepatocellular carcinoma (HCC) who have failed to improve during prior treatment with a drug called Sorafenib.
    A.4.1Sponsor's protocol code numberSGI-110-03
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01752933
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstex Pharmaceuticals Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstex Pharmaceuticals Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace
    B.5.2Functional name of contact pointJ L Cutter
    B.5.3 Address:
    B.5.3.1Street Address5375 Medpace Way
    B.5.3.2Town/ cityCincinnati, OH
    B.5.3.3Post code45227
    B.5.3.4CountryUnited States
    B.5.4Telephone number0015135799911
    B.5.6E-mailj.cutter@medpace.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code SGI-110
    D.3.4Pharmaceutical form Lyophilisate and solvent for suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSGI-110
    D.3.9.2Current sponsor codeSGI-110
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced Hepatocellular Carcinoma
    E.1.1.1Medical condition in easily understood language
    Liver cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10073071
    E.1.2Term Hepatocellular carcinoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the disease control rate at 16 weeks for subjects treated with SGI-110 after failure of sorafenib
    E.2.2Secondary objectives of the trial
    • To assess the safety and tolerability of SGI-110 treatment
    • To determine progression-free survival (PFS) and overall survival (OS) of SGI-110 treatment
    • To determine alpha fetoprotein (AFP) response to SGI-110 treatment
    • To determine the biological effect of SGI-110 on methylation of long interspersed nucleotide elements-1 (LINE-1) in blood and tumor tissue
    • To determine the pharmacokinetics (PK) of SGI-110 and decitabine in subjects with HCC
    • To determine the methylation status, and re-expression of silenced genes, in particular tumor suppressor genes (TSGs) such as RASSF1A, SFRP, MZB1, P16, and others, after SGI-110 treatment
    • To explore baseline mutation status of certain genes such as p53, or the methylation status of selected genes in tumor tissue before and after SGI-110 treatment as predictive of response to therapy
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects who are 18 years of age or older
    2. Subjects who have histological or cytological confirmed HCC, with advanced stage disease
    3. Subject with life expectancy of at least 16 weeks
    4. Subjects who have received prior sorafenib treatment, and showed evidence of disease progression, which is defined as Investigator verified radiologic progression, or intolerance of prior systemic therapy, which is defined as having had clinically significant adverse events that persisted despite one or more dose reductions or interruptions. Subjects may have received prior systemic therapy other than sorafenib, or other treatment for HCC such as embolization, chemoembolization, intra-arterial chemotherapy, ethanol injection, ablative therapy, cryosurgery, or other locoregional or targeted therapy.
    5. Subjects with ECOG performance status of 0-1
    6. Subjects with acceptable organ function, as evidenced by laboratory data:
    A. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5.0 X upper limit of normal (ULN)
    B. Total serum bilirubin ≤ 2 mg/dL
    C. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
    D. Platelets ≥ 75,000/mm3
    E. Serum creatinine levels ≤ 1.25 X ULN OR calculated (by Cockcroft-Gault formula)/measured creatinine clearance (CrCL) ≥ 50 mL/min
    F. Prothrombin time (PT) ≤ 6 sec above ULN, or international normalized ratio (INR) ≤ 2.3
    7. Subjects and their partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months following the last dose of study drug. Effective contraception includes methods such as oral contraceptives, double-barrier method (condom plus spermicide or diaphragm), or abstaining from sexual intercourse.
    8. Subjects who sign an approved informed consent form for the study
    9. Subjects who are willing and able to comply with the protocol and study procedures, in particular willingness to undergo tumor biopsy before (at baseline pretreatment), and after treatment with SGI-110 (Day 8 of Cycles 1 or 2)
    E.4Principal exclusion criteria
    1. Subjects who have known hypersensitivity to SGI-110
    2. Subjects who have received radiation therapy, other locoregional therapy, or chemotherapy within 4 weeks prior to the first dose of study drug. Subjects treated with sorafenib or other targeted agents must have been at least 2 weeks post treatment or at least 5 half-lives from last treatment. Subjects must have recovered from any significant toxicities associated with those therapies.
    3. Subjects who are at poor medical risk because of other systemic diseases or active uncontrolled infections
    4. Subjects with a life-threatening illness, medical condition or organ system dysfunction, or other reasons which, in the Investigator’s opinion, could compromise the subject’s safety, interfere with the metabolism of SGI-110, or compromise the integrity of the study outcomes
    5. Subjects with abnormal left ventricular ejection fraction (<50%) on echocardiogram or multiple-gated acquisition scan (MUGA)
    6. Subjects with uncontrolled ischemic heart disease or a history of congestive cardiac failure of ≥ Grade 3 severity according to New York Heart Association (NYHA)
    7. Subjects with known brain metastases
    8. Subjects with esophageal or gastric variceal bleeding within the last 6 months. Subjects at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened (using either esophagogastroduodenoscopy [EGD] or capsule endoscopy) for esophageal varices, unless such screening has been performed in the past one year from study entry and the subject is receiving medical treatment for prophylaxis of variceal bleeding, such as non-selective beta blockade. If varices are identified that require intervention (banding), the subject will not be eligible until varices are adequately treated.
    9. Subjects with clinically evident ascites (minimal, medically controlled ascites detectable on imaging studies only is allowed)
    10. Subjects with Child-Pugh C cirrhosis or Child-Pugh B cirrhosis with more than 7 points
    11. Subjects with encephalopathy in the last 6 months; however, subjects who are on stable dose or schedule of lactulose and/or neomycin and xifaxan are allowed
    12. Subjects with active hepatitis B infection not on adequate antiviral therapy13. Subjects with prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, non-metastatic prostate cancer with normal PSA or other cancer from which the subject has been disease free for at least three years
    14. Subjects with known history of human immunodeficiency virus (HIV)
    E.5 End points
    E.5.1Primary end point(s)
    Disease control rate at 16 weeks defined as percentage of subjects who achieve a best clinical response of complete response or partial response plus subjects who have stable disease at 16 weeks using RECIST v1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    16 weeks
    E.5.2Secondary end point(s)
    • The incidence and severity of adverse events (AEs)
    • DCR as defined above using modified RECIST (mRECIST) assessment for HCC
    • Percentage of subjects with AFP level reduction by 50% or more
    • Duration of response (DOR)
    • Progression-free survival (PFS)
    • Overall survival (OS)
    • Cmax, Cmin, AUC and other secondary PK parameters of SGI-110 and decitabine in during Cycle 1
    • Global DNA methylation (LINE-1 assay) in blood and in tumor tissue after SGI-110 treatment compared to baseline levels
    • Methylation status of selected genes (e.g. RASSF1A, SFRP, MZB1, P16, and others) in tumor tissue before and after SGI-110 treatment
    • Evaluation of methylation of circulating cell free DNA and analysis of mutation status of selected genes such as p53 in both tumor tissue and circulating tumor DNA.
    E.5.2.1Timepoint(s) of evaluation of this end point
    These are assessed at the end of participation. These are not critical to the analysis of results.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Korea, Republic of
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 25
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 21
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 46
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-11-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-03-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-08-20
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