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    The EU Clinical Trials Register currently displays   43974   clinical trials with a EudraCT protocol, of which   7311   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:2010-022416-40
    Sponsor's Protocol Code Number:3591
    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:2011-05-27
    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 number2010-022416-40
    A.3Full title of the trial
    A Translational, proof of the concept, study Of Pre-operative Pazopanib in treatment-naive patients with resectable soft tissue Sarcomas (TOPPS)
    A.3.2Name or abbreviated title of the trial where available
    Translational study Of Pre-operative Pazopanib in Sarcomas (TOPPS)
    A.4.1Sponsor's protocol code number3591
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorThe Royal Marsden NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Yes
    D.2.1.1.1Trade name Votrient
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxo Group Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 namepazopanib
    D.3.4Pharmaceutical form Coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNpazopanib
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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
    Resectable Soft Tisue Sarcomas (cancer of conective soft tissues)
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To asses the response to preoperative pazopanib in terms of tumour vascularity and blood flow (vascular responses) using functional (Dynamic Contrast Enhanced - DCE) magnetic resonance imaging (MRI).
    E.2.2Secondary objectives of the trial
    SECONDARY OBJECTIVES To assess vascular and cellular responses to preoperative pazopanib using other modalities of functional MRI (diffusion-weighted [DW-MRI] and blood oxygenation level-dependent [BOLD-MRI]. To assess the tolerability and toxicity profile of pazopanib given in the preoperative and postoperative settings in this population. To describe any radiological evidence of antitumour activity with neoadjuvant pazopanib by assessment of objective response using RECIST. To describe any histopathological evidence of antiangiogenic (loss of blood vessels) and antitumour activity with neoadjuvant pazopanib by examining the resected tumor specimens. To examine changes in angiogenesis (blood vessels growth) markers in tumor tissue after pre-operative treatment with pazopanib. EXPLORATORY OBJECTIVES To explore the value of monitoring early changes in circulating angiogenesis-related proteins during preoperative treatment with pazopanib. To explore the value of
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of written informed consent. 2. Age ≥ 18 years. 3. Confirmed histological diagnosis of intermediate-high grade STS: synovial sarcoma, leiomyosarcoma, myxofibrosarcoma, and others subtypes including angiosarcoma. 4. Stage I-III deemed suitable for surgical treatment, and naïve for either preoperative chemotherapy, radiotherapy, or any other molecularly targeted or experimental therapy. 5. Measurable tumor at least 3 cm in the longest diameter and suitable for magnetic resonance imaging (MRI) scanning and functional (DCE-, DW-, and BOLD) MRI studies. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Tumor tissue must be provided for all subjects for correlative biomarker studies before and at surgery (or progression if a patient is not finally deemed suitable for surgery). Pre-treatment samples could include tumor tissue obtained for other purposes, if the patient has not had any anticancer treatment between the biopsy and the start day on pazopanib. 8. Adequate bone marrow function as defined by: - Absolute neutrophil count (ANC) > 1.5 x10^9/L - Haemoglobin = or > 10 g/dL (without a transfusion within 7 days of screening assessment). - Platelets = or > 100 X 10^9/L 10. Adequate organs function as defined by: - Liver function: Total bilirubin <1.5 X UNL, ALT and AST  2.5 X UNL. - Renal function: Serum creatinine <1.5 mg/dL (133 µmol/L) (or if greater calculated creatinine clearance [Cockcroft-Gault formula] >50 mL/min, and normal urine protein to creatinine ratio (UPC) or if >1, then urinary protein excretion must be <1.5g in a 24 hr period. - Coagulation: Partial thromboplastin time (PTT), and prothrombin time (PT) or international normalized ratio (INR) < 1.2 X UNL. 10. A female is eligible to enter and participate in this study if she is of non-childbearing potential (i.e. physiologically incapable of becoming pregnant), including any female who has had: • A hysterectomy • A bilateral oophorectomy (ovariectomy) • A bilateral tubal ligation • Is post-menopausal Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L). Subjects using HRT must have experienced total cessation of menses for > 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow: • An intrauterine device with a documented failure rate of < 1% per year. • Vasectomized partner who is sterile prior to the female subject’s entry and is the sole sexual partner for that female. • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product. • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide). • Oral contraceptives • Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug 11. Patient must be able and willing to comply with treatment evaluations and follow up.
    E.4Principal exclusion criteria
    1. No prior diagnosis of other malignancies, except subjects who have had another malignancy and have been disease-free for 10 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. 2. History or clinical evidence of metastases, including central nervous system (CNS) metastases whether they have been treated or not. 3. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: • Active peptic ulcer disease • Known intraluminal metastatic lesion/s with risk of bleeding • Inflammatory bowel disease (e.g. ulcerative colitis, crohn's disease), or other gastrointestinal conditions with increased risk of perforation • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment. 6. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: • Malabsorption syndrome • Major resection of the stomach or small bowel. 5. Presence of uncontrolled infection. 6. Corrected QT interval (QTc) < 480 msecs using Fridericia’s formula 7. History of any one or more of the following cardiovascular conditions within the past 6 months: • Cardiac angioplasty or stenting • Myocardial infarction • Unstable angina • Coronary artery bypass graft surgery • Symptomatic peripheral vascular disease • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) 8. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by A minimum of 1 hour; on each of these occasions, the mean (of 3 readings) systolic blood pressure (SBP) / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study. 9. History of cerebrovascular accident including transient ischemic attack (TIA). 10. Patients who require anticoagulants are not eligible for this study. 11. History of pulmonary embolism or deep venous thrombosis (DVT) only if requiring anticoagulant treatment at the present. 12. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major). 13. Evidence of active bleeding or bleeding diathesis, and including hemoptysis of any cause within 6 weeks of first dose of study drug. 15. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. 16. Patients known to be allergic to gadolinium based MRI contrast agents or ineligibility for MRI scanning (for example metal implants such as cochlear implants, cardiac pacemakers, heart valves, aneurysm clips and metal fragments in eyes). 17. Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
    E.5 End points
    E.5.1Primary end point(s)
    The primary objective of TOPPS is to assess vascular tumor responses to short-term preoperative pazopanib by functional DCE-MRI parameters of tumor vasculature and blood flow such as Ktrans.
    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 No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    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 Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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 No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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
    4-12 weeks after the last trial participant receives the last dose of the investigational medicinal product (It will represent the end of study visit of the last patient on trial).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days15
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others Information not present in EudraCT
    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 0
    F.4.2.2In the whole clinical trial 0
    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)
    Research would finish once the last patient enrolled in the study has completed at least 12 months of postoperative adjuvant treatment with pazopanib or after completing 1-year follow-up in those patients who did not receive adjuvant pazopanib. Afterwards and once patients are off study, the continued care will be at the discretion of the treating physician.
    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 Decision2011-07-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-09-30
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2013-04-25
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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
    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.

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