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   43871   clinical trials with a EudraCT protocol, of which   7290   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:2020-004246-11
    Sponsor's Protocol Code Number:EDO-S101-1002
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-05-20
    Trial 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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2020-004246-11
    A.3Full title of the trial
    A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics and Efficacy of Tinostamustine, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Patients with Advanced Solid Tumors
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    This study will evaluate the safety, tolerability and efficacy of Tinostamustine in late-stage cancer patients. Different types of solid tumors will be treated with Tinostamustine. The study will be performed in multiple centers and countries.
    A.3.2Name or abbreviated title of the trial where available
    EDO-S101-1002
    A.4.1Sponsor's protocol code numberEDO-S101-1002
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02576496
    A.5.4Other Identifiers
    Name:INDNumber:125180
    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 SponsorMundipharma Research Limited
    B.1.3.4CountryUnited Kingdom
    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 supportMundipharma Research Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCromsource
    B.5.2Functional name of contact pointKarolina Kasztalska-Kazmierczak
    B.5.3 Address:
    B.5.3.1Street AddressGen. J. Zajaczka 32
    B.5.3.2Town/ cityWarszawa
    B.5.3.3Post code01-510
    B.5.3.4CountryPoland
    B.5.4Telephone number00482263333632
    B.5.6E-mailkarolina.kasztalska@cromsource.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 nameTinostamustine
    D.3.2Product code EDO-S101
    D.3.4Pharmaceutical form Lyophilisate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTINOSTAMUSTINE
    D.3.9.2Current sponsor codeEDO S101
    D.3.9.4EV Substance CodeSUB195193
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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
    • Cohort 1: Relapsed/refractory Small Cell Lung Cancer
    • Cohort 2: Relapsed/refractory Soft Tissue Sarcoma
    • Cohort 3: Relapsed/refractory Triple-Negative Breast Cancer
    • Cohort 4: Relapsed/refractory ovarian cancer
    • Cohort 5: Relapsed/refractory endometrial cancer
    On 05 March 2021 the Sponsor has taken the decision to halt
    recruitment into the Cohorts for relapsed/refractory triple-negative
    breast cancer (TNBC) and relapsed/refractory endometrial cancer on
    this study.
    E.1.1.1Medical condition in easily understood language
    "Relapse" means when a few of the original cancer cells survived the initial treatment. "Refractory" is a cancer that may be resistant at the beginning/becomes resistant during treatment.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10041071
    E.1.2Term Small cell lung cancer stage unspecified
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level LLT
    E.1.2Classification code 10084066
    E.1.2Term Triple negative breast cancer metastatic
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10033130
    E.1.2Term Ovarian cancer NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10014735
    E.1.2Term Endometrial cancer NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10002479
    E.1.2Term Angiosarcoma NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10057043
    E.1.2Term Dermatofibrosarcoma
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10015103
    E.1.2Term Epithelioid sarcoma NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10024193
    E.1.2Term Leiomyosarcoma NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10024631
    E.1.2Term Liposarcoma NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 22.1
    E.1.2Level LLT
    E.1.2Classification code 10082807
    E.1.2Term Solitary fibrous tumor
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10042866
    E.1.2Term Synovial sarcoma NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10025556
    E.1.2Term Malignant fibrous histiocytoma NOS
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10029276
    E.1.2Term Neurofibrosarcoma NOS
    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
    Evaluation of Response Rate in Selected Solid Tumor Cohorts. The Primary Objective of this study is to determine the objective response rate (ORR) [complete response (CR) plus partial response (PR)] of any duration, plus the rate of patients with stable disease (SD) of at least 4 months duration at a dose of 80 mg/m2 administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle.
    E.2.2Secondary objectives of the trial
    The Secondary Objectives of this study are:
    1) To evaluate safety and tolerability of 80 mg/m2 of Tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle.
    2) To determine the progression-free survival (PFS) time for patients who received 80 mg/m2 of Tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle.
    3) To determine the overall survival (OS) for patients who received 80 mg/m2 of Tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle.
    4) To determine duration of response.
    5) To establish the whole PK profiles of Tinostamustine.

    The Exploratory Objective is to correlate the extent of gene expression changes in tumor samples with anti-tumor activity.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Patient willing and able to sign the informed consent
    • Patients age ≥18 years at signing of the informed consent
    • Life expectancy > 3 months
    • Histologically confirmed diagnosis of advanced or metastatic solid
    tumors
    • Patients with secondary metastasis to the central nervous system (CNS) are eligible if they have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to trial day 1 and they meet all of the following criteria: (1) Residual neurological symptoms ≤ Grade 1 (2) No glucocorticoids requirement or patients may be receiving low doses of glucocorticoids providing the dose has been stable for at least 2 weeks prior to starting the trial medication (3) Follow-up imaging studies show no progression of treated lesions
    and no new lesions
    • Evaluable disease; measurable on imaging as assessed by RECIST
    version 1.1
    • ECOG performance status ≤2
    • ANC (polymorphonuclear [PMN] cells plus bands) >1,000/μL
    • Platelets ≥100,000/μL. . Platelet transfusions within the 14 days before
    Day 1 of Cycle 1 is prohibited.
    • AST/ALT ≤3× upper limit of normal (ULN). In cases with liver involvement ALT/ AST ≤5× ULN
    • Total bilirubin ≤1.5 mg/dL unless elevated due to known Gilbert’s
    syndrome
    • Creatinine ≤1.5 ULN
    • Serum potassium and magnesium at least at the lowest limit of
    normal (LLN) range, before every IMP administration. If it is below LLN, supplementation is permissible
    • Female study participants of child-bearing potential and their partners, and male study participants who intend to be sexually active with a woman of child-bearing potential, must be willing to use at least TWO highly effective forms of contraception
    Cohort 1:
    • Histologically or cytologically confirmed limited or extensive disease
    stage of SCLC
    • Received at least 1 line of prior combination chemotherapy or biological therapy and no other standard therapy with proven clinical benefit is available/recommended
    • At least 28 days should have elapsed since prior treatment as long as the patient has recovered from any related toxicities
    • Prior radiotherapy is acceptable the patient has recovered from any radiotherapy related acute toxicities
    • The disease progressing during/relapsing after the previous treatment
    • Presence of measurable disease as defined by RECIST version 1.1
    Cohort 2:
    • Histologically confirmed diagnosis of advanced, unresectable, or
    metastatic STS not amenable to curative treatment
    • Received at least 1 prior line chemotherapy or biological therapy regimen and no other standard therapy with proven clinical benefit is available or recommended. At least 28 days should have elapsed since prior chemotherapy as long as the patient recovered from any related
    toxicities
    • Disease progressing during or relapsing after the previous treatment
    • Presence of measurable disease as defined by RECIST version 1.1
    Cohort 3:
    RECRUITMENT INTO THIS COHORT HAS NOW BEEN HALTED

    Cohort 4:
    • Histologically or cytologically confirmed advanced ovarian cancer
    epithelial ovarian cancer including primary peritoneal cancer or fallopian tube cancer
    • At least 28 days should have elapsed since prior chemotherapy
    • Disease progressing during or relapsing after the previous treatment
    • Presence of measurable disease as defined by RECIST version 1.1
    Cohort 5:
    RECRUITMENT INTO THIS COHORT HAS NOW BEEN HALTED
    E.4Principal exclusion criteria
    • Patients with primary CNS cancer
    • Patients with QTc interval (Fridericia’s formula) >450 ms
    • Patients who are on treatment with drugs known to prolong the QT/QTc interval
    • Patients who are being treated with Valproic Acid for any indication (epilepsy, mood disorder)
    • Any serious medical condition that interferes with adherence to trial procedures
    • Prior history of another solid tumor malignancy diagnosed within the last 3 years of trial enrollment excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment)
    • Pregnant or breastfeeding women
    • New York Heart Association (NYHA) stage III/IV congestive heart failure (Section 13.2). The following arrhythmias: atrial fibrillation/flutter with poor rate control, documented sustained ventricular tachycardia (defined as >30 seconds or requiring cardioversion before 30 seconds have elapsed) or TdP
    • Significant co-morbidities (e.g., active infection requiring systemic therapy, history of human immunodeficiency virus [HIV] infection, or active Hepatitis B or Hepatitis C)
    • Use of other investigational agents or previous anticancer therapies within 28 days prior to the first dose of tinostamustine, provided the patient has recovered from any related toxicities ≥Grade 1
    • Steroid treatment within 7 days prior to trial treatment. Patients that require intermittent use of bronchodilators, topical steroids, or local steroid injections will not be excluded from the trial. Patients who have been stabilized to 10 mg prednisolone orally (PO) once daily (QD) (or equivalent), daily (or less) at least 7 days prior to IMP administration are allowed
    E.5 End points
    E.5.1Primary end point(s)
    Phase 2 is designed to determine the ORR plus the rate of patients with SD of at least 4 months duration of the RP2D (80 mg/m2 of tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Tumor response assessment by imaging will be performed at baseline and every 2 cycles during treatment and every 2 months after stopping treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
    To be translated
    E.5.2Secondary end point(s)
    The Secondary Objectives of this study are:
    1) To evaluate safety and tolerability of 80 mg/m2 of Tinostamustine
    administered over 1 hour on Day 1 and 15 of each 4-week treatment
    cycle
    2) To determine the progression-free survival (PFS) time for patients
    who received 80 mg/m2 of Tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle
    3) To determine the overall survival (OS) for patients who received 80
    mg/m2 of Tinostamustine administered over 1 hour on Day 1 and 15 of each 4-week treatment cycle
    4) To determine duration of response
    5) To establish the whole PK profiles of Tinostamustine

    The Exploratory Objective is to correlate the extent of gene expression changes in tumor samples with anti-tumor activity.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety evaluations will be performed at each study visit i.e. D1 and D15 of each treatment cycle.
    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 Yes
    E.6.10Pharmacogenetic Yes
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    United States
    Italy
    Netherlands
    Spain
    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 follow up visit of the last patient patient in the trial
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months36
    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: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 70
    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)
    Pt. who have discontinued participation for reasons other than PD will be assessed per RECIST 1.1 every 8 W (± 2 W) until documentation of PD or at start of subsequent anti-cancer therapy. Survival f-up: contact every 3 to 4 M for use of anti-cancer therapy/as survival until 1 Y after LSFV. Ongoing AE at Discontinuation Visit will be followed to resolution or stabilization. During f-up, any new SAE commencing within 30 D of Discontinuation Visit will be recorded and followed to resolution.
    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 Decision2021-05-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-09-30
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2023-03-29
    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-Sat May 04 01:49:35 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA