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   43845   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:2013-000762-11
    Sponsor's Protocol Code Number:62113-55115
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-08-22
    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 ConcernedGermany - BfArM
    A.2EudraCT number2013-000762-11
    A.3Full title of the trial
    A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in High Grade Uterine Sarcoma (HGUtS) after stabilization or response to doxorubicin +/- ifosfamide following surgery or in metastatic first line treatment
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in High Grade Uterine Sarcoma (HGUtS) after stabilization or response to doxorubicin +/- ifosfamide following surgery or in metastatic first line treatment
    A.4.1Sponsor's protocol code number62113-55115
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01979393
    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 SponsorEuropean Organisation for Research and Treatment of Cancer (EORTC)
    B.1.3.4CountryBelgium
    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 supportExelixis
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportEuropean Organisation for Research and Treatment of Cancer (EORTC)
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEuropean Organisation for Research and Treatment of Cancer (EORTC)
    B.5.2Functional name of contact pointRegulatory Affairs Department
    B.5.3 Address:
    B.5.3.1Street AddressAvenue E. Mounier 83/11
    B.5.3.2Town/ cityBrussels
    B.5.3.3Post code1200
    B.5.3.4CountryBelgium
    B.5.4Telephone number+3227741353
    B.5.5Fax number+3227727063
    B.5.6E-mailregulatory@eortc.org
    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 nameCabozantinib
    D.3.2Product code XL184
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    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 INNCABOZANTINIB
    D.3.9.1CAS number 1140909-48-3
    D.3.9.3Other descriptive nameCABOZANTINIB
    D.3.9.4EV Substance CodeSUB93452
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    High Grade Uterine Sarcoma (HGUtS)
    E.1.1.1Medical condition in easily understood language
    Uterine Sarcoma
    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 10046821
    E.1.2Term Uterine sarcoma 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
    The main objective of the trial is to assess, in High Grade Undifferentiated Uterine Sarcoma (HGUS), High Grade Endometrial Stromal Sarcoma (HGESS), High Grade Leiomyosarcomas (HGLMS) and High Grade (HG) adenosarcoma the activity (PFS at 4 months) of maintenance treatment with cabozantinib when compared with placebo after clinical benefit (CR, PR and SD) from standard chemotherapy (doxorubicin +/- ifosfamide) (given as an adjuvant treatment after curative surgery, or for locally advanced or metastatic disease).
    E.2.2Secondary objectives of the trial
    ♦ To assess the efficacy of maintenance treatment with cabozantinib when compared with placebo, using progression-free survival, overall survival, response rate, and duration of response among patients with measurable disease.
    ♦ To describe the safety profile of cabozantinib in patients with HGUS, HGESS, HGLMS and HG adenosarcoma
    ♦ To explore the response rate to chemotherapy in first line treatment for patients with measurable disease
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) At registration:
    Patients can be registered no earlier than 4 weeks prior to start of the 1st line treatment and no later than 4 weeks after last administration of 1st line treatment.
    - Patients who are suitable for treatment with doxorubicin +/- ifosfamide and fall within one of the following patient populations:
    ♦ HGUS, HGESS, HGLMS and HG adenosarcoma
    ♦ FIGO stage II and stage III : if adjuvant chemotherapy is proposed
    ♦ FIGO stage IV: if first line chemotherapy is proposed
    - 1 formalin fixed paraffin embedded block of tumor tissue is sent after registration of a patient. Histological central review is mandatory to confirm histology and grade.
    - Patients must be at least 18 years old
    - Before patient registration, written informed consent for central collection of tissue block or slides and any other trial-specific procedures must be obtained

    2) At Randomization
    Patients can be randomized within 12 weeks after last administration of 1st line treatment, before the start of protocol treatment
    - Central pathological confirmation: Histological evidence of HGUS, HGESS, HGLMS and HG adenosarcoma
    - Non-progressive patients (CR, PR, SD) after first line treatment and at time of randomization.
    - Patients able to swallow and retain oral tablets.
    - WHO/ECOG performance status 0-2
    - Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically non significant and/or stable on supportive therapy
    - The subject has organ and marrow function and laboratory values as follows before randomization
    . Absolute neutrophil count (ANC) ≥ 1500/mm3 without colony stimulating factor support for 7 days
    . Platelets ≥ 100,000/mm3
    . Hemoglobin ≥ 9 g/dL
    . Bilirubin ≤ 1.5 × the upper limit of normal. For subjects with known Gilbert’s disease, bilirubin ≤ 3.0 mg/dL
    . Serum albumin ≥ 2.8 g/dl
    . Serum creatinine ≤ 1.5 × the upper limit of normal or creatinine clearance (CrCl) ≥ 50 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72) × 0.85
    . Alanine aminotransferase and aspartate aminotransferase ≤ 3.0 × the upper limit of normal or ≤ 5.0 x ULN if liver metastases
    . Lipase < 2.0 × the upper limit of normal and no radiologic or clinical evidence of pancreatitis
    . Urine Dipstick: If Urine Dipstick ≥ 2+, determine Urine Protein to Creatinine Ratio (UPCR) by quantitative analysis; if UPCR ≥ 1, then a 24-hour urine protein must be assessed. Any patient with protein > 150 mg over 24 hours would not be eligible.
    . Serum phosphorus, calcium, magnesium and potassium ≥ lower limit of normal
    . Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 × the upper limit of normal
    - Clinically normal cardiac function based on the institutional lower limit of normal (LVEF assessed by MUGA or ECHO), normal 12 lead ECG (no prolongation of corrected QT interval (QTc) > 500 msecs according to Fridericia's formula) and no history of any one or more of the following cardiovascular conditions within the past 6 months:
    . Cardiac angioplasty or stenting
    . Clinically-significant cardiac arrhythmias
    . 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
    - Minor surgery within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study trt is permitted.
    - Women of child bearing potential must have a negative serum/urine pregnancy test within 3 days prior to the first dose of study treatment. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
    - Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 4 months after the last study treatment.
    - Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 8 weeks after the last study treatment.
    - Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
    E.4Principal exclusion criteria
    At Registration
    ♦ The following tumor types are NOT eligible: low-grade ESS, leiomyosarcoma (low or intermediate), carcinosarcoma, low-grade adenosarcoma, rhabdomyosarcoma (alveolar or embryonal) and soft tissue PNET of uterus/cervix.

    At randomization
    - Prior treatment with cabozantinib
    - history of congenital long QT syndrome
    - concurrent severe, clinically relevant hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
    - patient with concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;
    - concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors
    - patients who have suffered a cerebrovascular accident at any time in the past, patients who have suffered a transient ischemic attack in the past 6 months, patients who have suffered a deep venous thrombosis or a pulmonary embolism in the past 6 months
    note: Patients with recent DVT who have been treated with therapeutic anti-coagulating agents and remained stable for at least 6 weeks are eligible: subjects with a venous filter are not eligible for this study
    - Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
    - "known" intra-abdominal tumor/metastases invading GI mucosa
    - active peptic ulcer disease,
    - inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
    - malabsorption syndrome
    - Ongoing visceral complications from prior therapy
    - Prior gastrointestinal surgery
    ♦ Any of the following within 6 months before the first dose of study treatment:
    - abdominal or vaginal fistula
    - gastrointestinal perforation
    - bowel obstruction or gastric outlet obstruction
    - intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating study treatment even if the abscess occurred more than 6 months before the first dose of study treatment.
    - clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
    - patients with evidence of tumor invading the GI tract or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of study treatment
    - patients with radiographic evidence of cavitating pulmonary lesion
    - patients with tumor in contact with, invading or encasing any major blood vessels.
    - patients evidence of tumor invading the GI tract, or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of study trt
    - evidence of active bleeding or bleeding diathesis.
    - hemoptysis ≥ 0.5 teaspoon of red blood within 3 months before the first dose of study treatment. Note: Any patient with a prior history of hemoptysis associated with metastatic disease must have a bronchoscopy to rule out endobronchial lesions. A patient with an endobronchial lesion
    - signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
    - Major surgery or trauma within 12 weeks prior to first dose of study drug and/or presence of any non-healing wound, fracture or ulcer. Complete wound healing from major surgery must have occurred one month before the first dose of study treatment.
    - clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
    - Patients with clinically relevant ongoing complications from prior surgery .
    - concurrent or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4/5
    - contraindications to cabozantinib
    - planned use of chemotherapy, radiation therapy, radionuclide treatment, small molecule TKI or hormonal therapy, and any other investigational agent during the treatment period.
    - poor oral hygiene or invasive dental or orofacial procedures within 28 days before the first dose of study treatment.
    Prior radiation therapy
    ♦ radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 42 weeks before the first dose of study treatment. Patient must have fully healed and there are no ongoing sequelae from the previous radiation therapy before the first dose of study treatment.
    ♦ systemic treatment with radionuclides within 6 weeks before the first dose of study treatment.
    ♦ Patients with clinically relevant ongoing complications from prior radiation therapy
    - other malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome
    E.5 End points
    E.5.1Primary end point(s)
    Progression free survival rate
    E.5.1.1Timepoint(s) of evaluation of this end point
    at 4 months after randomization to cabozantinib or placebo
    E.5.2Secondary end point(s)
    1. Progression free survival rate
    2. Overall survival
    3. response rate and duration of response to cabozantinib
    4. Response rate to doxorubicin-based chemotherapy after registration on trial for the patients with measurable disease
    5. Quality of life (QoL)
    6. Safety of cabozantinib in HGUS, HGESS, HGLMS and HG adenosarcoma
    E.5.2.1Timepoint(s) of evaluation of this end point
    1+2+3+4: prior to registration; prior to randomization; every 8 weeks during the first year of the maintenance period, then every 12 weeks; within 30 days after last dose (if no progression since randomization)
    5. prior to registration; prior to randomization; within 3 days prior to each cycle, every 8 weeks during the first year of the maintenance period, then every 12 weeks; within 30 days after last dose
    6. as of randomization, continuously per event up to 30 days after last dose; for patient who cross-over to cabozantinib after progression: every 4 weeks until further progression
    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 No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 EEA27
    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
    United States
    Belgium
    France
    Germany
    Italy
    Netherlands
    Spain
    E.8.7Trial has a data monitoring committee Yes
    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
    End of study occurs when all of the following criteria have been satisfied:
    -Thirty days after all patients have stopped protocol treatment.
    -The trial is mature for the analysis of the primary endpoint as defined in the protocol, ie. all randomized patients have adequate follow-up to determine their PFS status at 4 months.
    -The database has been fully cleaned and frozen for this analysis.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years6
    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: 95
    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 No
    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 86
    F.4.2.2In the whole clinical trial 115
    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)
    After progression:
    - Cabozantinib arm: the treatment will be left to the discretion of the treating physician.
    - Placebo arm: patients may receive cabozantinib.

    Patients discontinuing therapy in the absence of progression should not receive any other cancer treatment before their disease progresses, unless this is clearly not in the interest of the patient.
    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 Decision2014-11-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2024-01-15
    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-Fri Apr 19 08:41:04 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA