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    Summary
    EudraCT Number:2011-003308-18
    Sponsor's Protocol Code Number:MO27782
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-04-25
    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 ConcernedGermany - PEI
    A.2EudraCT number2011-003308-18
    A.3Full title of the trial
    A two-cohort, open-label, multicenter Phase II trial assessing the efficacy and safety of pertuzumab given in combination with trastuzumab and vinorelbine in first line patients with HER2-positive advanced (metastatic or locally advanced) breast cancer.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A two-cohort Phase II study of pertuzumab, trastuzumab and vinorelbine in patients with HER2-positive breast cancer.
    A.3.2Name or abbreviated title of the trial where available
    VELVET
    A.4.1Sponsor's protocol code numberMO27782
    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 SponsorF. Hoffmann-La Roche Ltd.
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffmann-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 namePertuzumab (rhuMAb 2C4)
    D.3.2Product code RO 4368451/F01
    D.3.4Pharmaceutical form Concentrate 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 INNPertuzumab
    D.3.9.1CAS number 380610-27-5
    D.3.9.2Current sponsor codeRO4368451
    D.3.9.3Other descriptive namerhuMAb 2C4
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number420 mg / 14ml
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Bendarelbin
    D.2.1.1.2Name of the Marketing Authorisation holderBendalis GmbH
    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 nameVinorelbine
    D.3.4Pharmaceutical form Concentrate 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 INNVINORELBINE
    D.3.9.1CAS number 71486-22-1
    D.3.9.4EV Substance CodeSUB00069MIG
    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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Herceptin
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Ltd., UK
    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.3.4Pharmaceutical form Powder for concentrate for solution for injection/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 INNTRASTUZUMAB
    D.3.9.1CAS number 180288-69-1
    D.3.9.2Current sponsor codeRO 45-2317
    D.3.9.4EV Substance CodeSUB12612MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HER2-positive advanced (metastatic or locally advanced) breast cancer
    E.1.1.1Medical condition in easily understood language
    HER2-positive advanced breast cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10065430
    E.1.2Term HER-2 positive breast cancer
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare objective overall response rates (ORR) assessed
    by a blinded independent review committee (IRC) of pertuzumab given in combination with trastuzumab together in a single infusion bag (followed by vinorelbine) versus conventional sequential administration in separate infusion bags.
    E.2.2Secondary objectives of the trial
    o ORR assessed by the investigator
    o Time to response assessed by IRC and investigator
    o Duration of response assessed by IRC and investigator
    o Progression free survival (PFS)
    o Time to progression (TTP)
    o Overall survival (OS)
    o Safety and tolerability
    o Quality of life (EQ-5D and FACT-B questionnaires)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed written informed consent approved by the relevant Institutional Ethical Review Board (IRB).
    2. Female or male patients aged 18 years or older.
    3. Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection.
    4. HER2-positive (defined as either immunohistochemistry
    [IHC] 3+ or in situ hybridization [ISH] positive) as assessed by local laboratory on primary or metastatic tumor (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests, a HER2 gene count greater than 4).
    5. At least one measurable lesion and/or non-measurable
    disease evaluable according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (Eisenhauer et al. 2009).
    6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
    7. Left ventricular ejection fraction (LVEF) of at least 55%.
    8. Negative pregnancy test in women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization).
    9. For women of childbearing potential who are sexually active, agreement to use a highly effective, nonhormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-study treatment.
    10. Fertile males willing and able to use effective nonhormonal
    means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months post-study treatment.
    11. Life expectancy of at least 12 weeks.
    E.4Principal exclusion criteria
    1. Previous systemic non-hormonal anticancer therapy in the
    metastatic or locally advanced breast cancer setting. Note: Prior to study entry, up to two lines of hormonal therapy for metastatic or locally recurrent disease are permitted, one of which may be in combination with everolimus.
    2. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or
    lapatinib in the adjuvant or neoadjuvant setting.
    3. Disease progression while receiving trastuzumab and/or
    lapatinib in the adjuvant or neoadjuvant setting.
    4. Disease-free interval from completion of adjuvant or neo-adjuvant systemic non-hormonal treatment to recurrent disease of less than 6 months.
    5. History of persistent Grade 2 or higher (NCI-CTC, Version
    4.0) hematological toxicity resulting from previous adjuvant
    or neoadjuvant therapy.
    6. Patient with radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or
    magnetic resonance imaging (MRI) that are not well controlled (symptomatic or requiring control with continuous corticosteroid therapy [eg dexamethasone]) Note: Patients with CNS metastases are permitted to participate in the study if the CNS metastases are medically well controlled prior to screening (as assessed by the investigator) after receiving local therapy (irradiation, surgery etc) but without anti-HER2 therapy.
    7. Current peripheral neuropathy of Grade 3 or greater
    (NCI-CTC, Version 4.0).
    8. History of other malignancy (other than bilateral or previously diagnosed HER2-positive mBC) within the last 5 years, except
    for carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, or cancers with a similar curative outcome as those mentioned above.
    9. Serious uncontrolled concomitant disease that would
    contraindicate the use of any of the investigational drugs
    used in this study or that would put the patient at high risk for
    treatment-related complications.
    10. Inadequate organ function, evidenced by the following laboratory results:
    • Absolute neutrophil count <1,500 cells/mm3
    • Platelet count <100,000 cells/mm3
    • Hemoglobin <9 g/dL
    • Total bilirubin greater than upper limit of normal (ULN) (unless the patient has documented Gilbert’s syndrome)
    • Aspartate aminotransferase AST; SGOT) or alanine aminotransferase (ALT; SGPT) >2.5 × ULN (>5 x ULN in patients with liver metastases)
    • Alkaline phosphatase levels > 2.5 x ULN (>5 x ULN in patients with liver metastased, or > 10 x ULN in patients with bone metastases)
    • AST (SGOT) or ALT (SGPT) >1.5 × ULN with concurrent serum alkaline phosphatase >2.5 × ULN
    • Serum creatinine >2.0 mg/dL or 177 ╬╝mol/L
    • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic coagulation)
    11. Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: including but not limited to cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study treatment, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, serious cardiac arrhythmia requiring medication or other cardiovasclar problem that is uncontrolled or is currently controlled with medication.
    12. Current known infection with HIV, HBV, or HCV.
    13. Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy.
    14. Major surgical procedure or significant traumatic injury within 14 days prior to enrollment into the study or anticipation of need for major surgery during the course of study treatment. Note: Should surgery be necessary during the course of the study, patients should be allowed to recover for a minimum of 14 days prior to subsequent pertuzumab and trastuzumab treatment.
    15. Receipt of intravenous (IV) antibiotics for infection within 7 days prior to enrollment into the study.
    16. Current chronic daily treatment (continuous for > 3 months) with corticosteroids (dose
    equivalent to or greater than 10 mg/day methylprednisolone),
    excluding inhaled steroids.
    17. Known hypersensitivity to any of the study treatments or to
    excipients of recombinant human or humanized antibodies.
    18. History of receiving any investigational treatment within 28 days prior to enrollment into the study.
    19. Concurrent participation in any other therapeutic clinical trial.
    20. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    ORR assessed by IRC according to RECIST version 1.1, based on the best (confirmed) overall response (BOR; defined as the best response recorded from the start of trial treatment until disease
    progression/recurrence or death).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Analysis of the primary endpoint will be performed at the end of study for each cohort.
    E.5.2Secondary end point(s)
    • BOR as assessed by the investigator
    • Time to and duration of response (in responders) as assessed by the Investigator
    and IRC
    • PFS
    • TTP
    • OS
    E.5.2.1Timepoint(s) of evaluation of this end point
    The end of study is defined for each cohort as the time when all patients have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort unless they have been lost to follow-up, withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor whichever occurs first. Final analysis of PFS, and TTP and OS will also be performed at this time.
    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 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 Yes
    E.6.13.1Other scope of the trial description
    Quality of life, tolerability, optional translational research
    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 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) Yes
    E.8.2.2Placebo No
    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 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 concerned20
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA57
    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
    Brazil
    European Union
    United States
    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
    The study will end for each cohort when all patients have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, unless they have been lost to follow-up, withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor, whichever occurs first.
    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 months8
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months8
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 110
    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 state80
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 161
    F.4.2.2In the whole clinical trial 210
    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)
    Patients who discontinue study treatment for progressive disease or other reasons will receive treatment according to local standard of care. Any post-study anticancer therapies, information on patient outcomes, and post-progression anticancer therapies will be recorded in the eCRF during study FU period as reasonably possible. Roche will continue to provide pertuzumab to patients who are still receiving the IMP at the end of the study and are willing and suitable to enter an extension study.
    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 Decision2012-08-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-06-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-10-15
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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