Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43843   clinical trials with a EudraCT protocol, of which   7282   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2014-001862-84
    Sponsor's Protocol Code Number:ISO-CC-005
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2016-09-13
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2014-001862-84
    A.3Full title of the trial
    An Open-label, Multiple-site, Phase I/II Dose Cohort Trial of [6R] 5,10-Methylene Tetrahydrofolate (Modufolin®) in Combination with a Fixed Dose of 5-Fluorouracil (5-FU) alone or together with a Fixed Dose of Oxaliplatin or Irinotecan in Patients with Stage IV Colorectal Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open-label, Multiple-site, Phase I/II Dose Cohort Trial of [6R] 5,10-Methylene Tetrahydrofolate (Modufolin®) in Combination with a Fixed Dose of 5-Fluorouracil (5-FU) alone or together with a Fixed Dose of Oxaliplatin or Irinotecan in Patients with Stage IV Colorectal Cancer
    A.4.1Sponsor's protocol code numberISO-CC-005
    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 SponsorIsofol Medical AB
    B.1.3.4CountrySweden
    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 supportIsofol Medical AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIsofol Medical AB
    B.5.2Functional name of contact pointLisa Skintemo
    B.5.3 Address:
    B.5.3.1Street AddressArvid Wallgrens backe 20
    B.5.3.2Town/ cityGöteborg
    B.5.3.3Post codeSE-413 46
    B.5.3.4CountrySweden
    B.5.4Telephone number+46 (0)70 2 43 37 65
    B.5.6E-maillisa.skintemo@isofolmedical.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.3.1Product nameModufolin® powder for solution for injection 100 mg
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous bolus use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNModufolin API
    D.3.9.2Current sponsor codeModufolin API
    D.3.9.3Other descriptive name(6R)-5,10-methylene-tetrahydrofolic acid
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 metastatic colorectal cancer (stage IV)
    E.1.1.1Medical condition in easily understood language
    Colon cancer that has spread to other organs.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10010035
    E.1.2Term Colorectal cancer stage IV
    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
    The primary objective is:
    • To characterise the tolerability of Modufolin in Stage IV CRC patients in 1st or 2nd line treatment in terms of toxicity during eight (8) weeks of treatment with one (1) of four (4) dose levels of Modufolin in the given treatment arms.
    E.2.2Secondary objectives of the trial
    - To characterise all adverse events (AEs) and clinically significant abnormal laboratory test result changes regardless of attribution during the entire study period.
    - To evaluate tumour response and disease progression by means of Objective Response Rate (ORR) and Early Tumour Shrinkage (ETS) at the end of study participation.
    - To determine the pharmacokinetic characteristics of methylenetetrahydrofolate (MTHF), methyl-tetrahydrofolate (methyl-THF), and tetrahydrofolate (THF) calculated from plasma samples in each cohort following Modufolin® administration on Day 1 in Cycle #1 and in Cycle #4 in a subset of patients.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Follow-up Study of Clinical Study ISO-CC-005:
    After end of study participation, patients that may benefit from continued treatment with Modufolin® will be offered enrolment in a Follow-up Study, provided they fulfil the eligibility criteria for enrolment. Upon enrolment in the Follow-up Study, patients will continue treatment with Modufolin® in accordance with the assigned Main Study regimen, which may be adapted with additional treatment at the discretion of the Investigator. In this way, the Sponsor aims to meet patients’ specific needs and facilitate investigators the possibility to follow clinical practice. For patients in Cohorts #18b and #19b: The frequency of the CT/MRI scan evaluations will be mandatory and occur every eight (8) to 12 weeks (±3 days) since previous scan was performed.
    E.3Principal inclusion criteria
    1) Advanced metastatic colorectal (Stage IV) cancer verified by biopsy, eligible for 1st or 2nd line therapy. For enrolment in Cohorts #18a and
    #18b of Treatment Arm #4 and in Treatment Arm #6: only patients eligible for 1st line therapy.
    2) CT-scan or MRI of thorax, abdomen and pelvis; within five (< 5) weeks before start of chemotherapy
    3) Evaluable disease and one measurable site of disease according to RECIST 1.1 criteria (at least 10 mm for CT-scan or MRI)
    4) Male and female adults, age of 18 years or older
    5) WHO performance status 0 < 2, and life expectancy > 3 months
    6) Adequate haematological function:
    a) Haemoglobin (Hb) > 100 g/L,
    b) Absolute neutrophil count (ANC) > 1.5x109/L, and
    c) Platelets > 100x109/L
    7) Adequate renal and hepatic functions:
    a) Creatinine clearance > 50 mL/min,
    b) Total bilirubin < 1.5 times upper limit of normal (ULN),
    c) Aspartate transaminase (AST) and Alanine transaminase (ALT) < 3 times ULN (and < 5 times ULN in case of liver metastases)
    8) Eligible for at least one of the chemotherapy treatment arms in the study protocol which, at the time of enrolment, is currently open for
    recruitment, according to Investigators judgement
    9) Negative pregnancy test for females of child bearing potential
    10) Willing and able to provide informed consent
    11) Using adequate contraceptive measures
    Female patients who have been post-menopausal for more than one year or female patients of childbearing potential using a highly efficient method of contraception (i.e. a method with less than 1% failure rate [e.g. sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomised partner]).
    Male patients agreeing to use condoms during the study and for three months after the end of the study/last dose of the investigational medicinal product (IMP), or patients having a partner who is using a highly efficient method of contraception as described above.
    E.4Principal exclusion criteria
    1) Malign tumours other than colorectal adenocarcinomas (current or within the previous 5 years), with the exception for curatively treated non melanoma skin cancer or in situ carcinoma of the cervix
    2) Fewer than 14 days since start of administration of latest treatment of CRC and first study drug dosing in the Main Study. For enrolment in
    Cohort #18b of Treatment Arm #4 and Cohort #19b of Treatment Arm #6, only: Less than 6 months between randomization and completion of
    the last anti-cancer treatment (such as chemotherapy/radiotherapy/immunotherapy). B: Rectal cancer treatment shorter than 8 weeks of chemo/radiation therapy is allowed.
    3) Evidence of central nervous system metastases
    4) Unresolved bowel obstruction or sub-obstruction, uncontrolled Crohn’s disease or ulcerative colitis
    5) History of cardiac disease with a New York Heart Association (NYHA) Class II or greater congestive heart failure, myocardial infarction or unstable angina in the past six (6) months prior to Day 1 of treatment and serious arrhythmias requiring medication for treatment
    6) Current severe chronic diarrhoea
    7) Current chronic infection or uncontrolled serious illness causing immunodeficiency
    8) Any current uncontrolled serious illness or medical condition
    9) Current major psychiatric disorder (e.g. major depression, psychosis)
    10) Participation in another clinical study with an IMP within one (1) month prior to inclusion
    11) Known intolerance to fluoropyrimidine therapy suggestive of dihydropyrimidine dehydrogenase deficiency
    12) Suspicion of hypersensitivity or allergy to the IMP, or to products chemically related to the IMP (i.e. folate derivatives)
    13) Female patients: currently pregnant or breast-feeding
    14) Previous treatment with Modufolin® at any dose, regardless of indication treated.
    15) Suspicion, as per Investigator's judgement, of forthcoming need of any chemotherapeutic agents, antibodies or biologics other than those included in this protocol.
    16) For enrolment in Cohort #18b of Treatment Arm #4 and Cohort #19b of Treatment Arm #6, only: Confirmation of progressive disease within 6
    months after completion of prior adjuvant anti-cancer treatment.
    E.5 End points
    E.5.1Primary end point(s)
    - Number and severity of dose limiting toxicity (DLT) associated with the administration of the chemotherapeutic agents given or any other
    significant AEs at the respective Modufolin® dose level in each treatment arm of the study.
    - Number of patients with chemotherapeutic agent dose adjusted (including withdrawal of therapy agent) due to presence of related
    toxicity at the respective Modufolin® dose level in each treatment arm of the study.
    - Number of adjustments required for any administered chemotherapeutic agent due to presence of related toxicity, at the respective Modufolin® dose level in each treatment arm of the study.
    E.5.1.1Timepoint(s) of evaluation of this end point
    8 weeks
    E.5.2Secondary end point(s)
    - Number and severity of AEs or clinically significant abnormal laboratory test result changes regardless of causal relationship
    - Determination of Objective Response Rate (ORR) and Early Tumour Shrinkage (ETS) after four (4) cycles of chemotherapy.
    - Plasma pharmacokinetics of 5,10- Methylene Tetrahydrofolate (MTHF), 5-Methyl Tetrahydrofolate (5-methyl-THF), and Tetrahydrofolate (THF), directly prior to, and at 10 minutes, at 1, 2, and 4 hours in each cohort following Modufolin® administration on Day 1 in Cycle #1 and in Cycle #4 in a subset of patients.
    E.5.2.1Timepoint(s) of evaluation of this end point
    8 weeks
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Modufolin® has been tested before, first time in combination with 5-FU, Oxilaplatin and Irinotecan
    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 Yes
    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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial6
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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 No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    Last patient, last visit. End of study participation is defined as the date of the patient's last visit in the study by completing End-of-Study Visit in the Main Study. For patients that are enrolled in the Followup Study, the end of study participation is defined as the date when patient completes the End of Follow-up Study.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days16
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days28
    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: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 90
    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 state17
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 135
    F.4.2.2In the whole clinical trial 135
    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)
    Enrolment in Follow-up Study of Clinical Study ISO-CC-005 or Standard care.
    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 Decision2016-10-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-10-11
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-01-30
    For support, Contact us.
    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 18 07:58:14 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA