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    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7294   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2017-004112-19
    Sponsor's Protocol Code Number:POLARIS2013-001
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2017-12-11
    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 number2017-004112-19
    A.3Full title of the trial
    Phase 1-2 Study of ADI-PEG 20 plus FOLFOX in Subjects with
    Advanced Gastrointestinal Malignancies Focusing on Hepatocellular Carcinoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 1-2 Study in Patients with Advanced Gastrointestinal Malignancies Focusing on Hepatocelluar Carcinoma, to determine the treatment effect of ADI-PEG 20 given in combination with chemotherapy drugs folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX).
    A.3.2Name or abbreviated title of the trial where available
    Phase 1-2 Study of ADI plus FOLFOX in GI cancer focusing on HCC
    A.4.1Sponsor's protocol code numberPOLARIS2013-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02102022
    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 SponsorPolaris Pharmaceuticals, Inc.
    B.1.3.4Country
    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 supportPolaris Pharmacueticals, Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPolaris Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointStella Feng
    B.5.3 Address:
    B.5.3.1Street Address9373 Towne Centre Drive, Suite 150
    B.5.3.2Town/ citySan Diego
    B.5.3.3Post code92121
    B.5.4Telephone number1-8584526688
    B.5.5Fax number1-8584523199
    B.5.6E-mailsfeng@polarispharma.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/05/289
    D.3 Description of the IMP
    D.3.1Product nameADI-PEG 20
    D.3.2Product code ADI-PEG 20
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPegargiminase
    D.3.9.1CAS number 1394129-74-8
    D.3.9.2Current sponsor codeADI-PEG 20
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10.5 to 12.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated

    Advanced hepatocellular carcinoma (HCC)in the third line or later setting
    E.1.1.1Medical condition in easily understood language

    Hepatocellular Carcinoma is the most common type of liver cancer and occurs often in people with chronic liver disease
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10049010
    E.1.2Term Carcinoma hepatocellular
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial

    The purpose of this study is to determine effectiveness of study treatment by looking at the response rate when ADI-PEG 20 is given in combination with folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX).
    E.2.2Secondary objectives of the trial

    The secondary objectives are to determine:
    - Progression free survival (the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse)
    - Overall survival (the length of time from the start of treatment for a disease that patients diagnosed with the disease are still alive)
    - Duration of response (time from documentation of tumor response to disease progression)
    - Disease control rate (proportion of patients with reduction in tumor burden of a predefined amount)
    - Pharmacodynamics (how the drug affects the body)of ADI-PEG 20 in combination with FOLFOX
    - Pharmacokinetics (how the body affects the drug) of ADI-PEG 20 in combination with FOLFOX
    - Immunogenicity (ability to cause an immune response)of ADI-PEG 20 in combination with FOLFOX
    - Change of Alpha-fetoprotein (a type of protein associated with liver cancer)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Advanced histologically or cytologically proven HCC (except with prior liver transplantation).
    2. Treatment with at least 2 prior systemic therapy regimens.
    3. Child-Pugh grade A. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period.
    4. Measurable disease using RECIST 1.1 criteria. At least 1 measurable lesion must be present. Subjects who have received local-regional therapies are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan.
    5. ECOG performance status of 0 - 1.
    6. Expected survival of at least 3 months.
    7. Age ≥ 18 years.
    8. Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment. Surgery or procedure for placement of vascular access devices is exempt from this period.
    9. Subjects must agree to use at least one form of highly effective contraception or agree to refrain from intercourse for the duration of the study. Contraceptive use must be continued until at least 30 days after the last administration of ADI-PEG 20 and at least 90 days after the last administration of FOLFOX. For female subjects, a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If HCG pregnancy test is positive, further evaluation to rule out pregnancy must be performed according to GCP before this patient is claimed eligible.
    10. Informed consent must be obtained prior to study initiation.
    11. No concurrent investigational studies are allowed.
    12. Total bilirubin < 1.5 x upper limit of normal range.
    13. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal range.
    14. Absolute neutrophil count (ANC) > 1500/μL.
    15. Platelets > 75,000/μL.
    16. Serum uric acid ≤ 8 mg/dL (with or without medication control).
    17. Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine >1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 60 mL/min/1.73 m2 (calculated using the Jelliffe equation: calculated creatinine clearance = 98 - 0.8 [age (yrs.) - 20] /serum creatinine (x 0.9 if female).
    18. Brain metastases are allowed if well controlled and without seizures.
    19. Serum albumin level ≥ 2.8 g/dL.
    20. Prothrombin time (PT)-international normalized ratio (INR): PT <6 seconds above control or INR <1.7. Subjects on Coumadin anti-coagulants are to receive only 1 point for their INR status.
    21. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.
    E.4Principal exclusion criteria
    1. Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
    2. Pregnancy or lactation.
    3. Expected non-compliance.
    4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness.
    5. Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline (except alopecia) or ≤ Grade 1 AEs, or deemed irreversible from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a safety risk by the Sponsor and investigator may be allowed upon agreement with both.
    6. Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome.
    7. Subjects who had been treated with ADI-PEG 20 previously.
    8. History of seizure disorder not related to underlying cancer.
    9. Known HIV positivity (testing not required).
    10. Known allergy to pegylated compounds.
    11. Known allergy to E. coli drug products (such as GMCSF).
    12. Known allergy to oxaliplatin or other platinum compounds.
    13. Prior grade 2 or higher neuropathy from prior platinum unless neuropathy is currently ≤ grade 1.
    14. Contraindications to fluorouracil:
    a. Subjects with poor nutritional state.
    b. Known depressed bone marrow function.
    c. Subjects with potentially serious infections.
    d. Known allergy to fluorouracil.
    E.5 End points
    E.5.1Primary end point(s)
    The number and percent of subjects who exhibit each level of tumor response will be summarized. Best overall response with confidence intervals will also be determined.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Scans are to be performed every 8 weeks in the week after every 8th dose of study drug for the first year of treatment, and every 12 weeks through the second year of treatment. In case of tumor response (CR, PR), repeat imaging study at 4 weeks is to be performed to confirm response. Subjects then return to scans every 8 weeks from the confirmatory scan through the first year of treatment, and then every 12 weeks in the second year of treatment.

    A futility analysis will be included. Futility will be assessed three times during the study based on having ORR data available for 56, 110, and 166 patients.
    E.5.2Secondary end point(s)

    PFS, OS, DoR, DCR, pharmacodynamics, pharmacokinetics, immunogenicity, and AFP will be summarized.
    E.5.2.1Timepoint(s) of evaluation of this end point

    The secondary objectives of the phase 2 will be analyzed at the end of the final analysis.
    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 Yes
    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 Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    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 No
    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.8.2.4Number of treatment arms in the trial1
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    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
    China
    France
    Germany
    Italy
    Taiwan
    United Kingdom
    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 years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days31
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 134
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 91
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 225
    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)

    At the current time there are no plans to make treatment available to patients beyond the sope of the protocol.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation NA
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-01-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-10
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-03-24
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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