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    Summary
    EudraCT Number:2011-000661-12
    Sponsor's Protocol Code Number:OCTO_022
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-07-14
    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 number2011-000661-12
    A.3Full title of the trial
    A randomised double blind phase 2 trial of whole brain radiotherapy with or without vandetanib in metastatic melanoma with brain metastases
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of vandetanib in combination with whole brain radiotherapy in the treatment of metastatic melanoma which has spread to the brain.
    A.3.2Name or abbreviated title of the trial where available
    XRT +/- vandetanib in CNS melanoma
    A.4.1Sponsor's protocol code numberOCTO_022
    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 SponsorUniversity of Oxford
    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 supportAstraZeneca
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationOncology Clinical Trials Office (OCTO)
    B.5.2Functional name of contact pointRADVAN Trial Coordinator
    B.5.3 Address:
    B.5.3.1Street AddressUniversity of Oxford, Old Road Campus Research Building, Roosevelt Drive
    B.5.3.2Town/ cityOxford
    B.5.3.3Post codeOX3 7DQ
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01865617089
    B.5.5Fax number01865617010
    B.5.6E-mailRADVAN@octo-oxford.org.uk
    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 nameVandetanib
    D.3.2Product code ZD6474
    D.3.4Pharmaceutical form 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 INNVandetanib
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 placeboTablet
    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
    Metastatic melanoma with brain metastases.
    E.1.1.1Medical condition in easily understood language
    Melanoma skin cancer which has spread to the brain.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level LLT
    E.1.2Classification code 10006128
    E.1.2Term Brain metastases
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The principal objective of this study is to evaluate how long whole brain radiotherapy plus vandetanib is able to control the progression of melanoma brain metastases, compared with radiotherapy alone.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are to further evaluate the effectiveness of whole brain radiotherapy plus vandetanib compared with radiotherapy alone in patients with melanoma brain metastases in terms of: 1. maintenance of cognitive function. 2. control of disease at 6 months following start of treatment. 3. duration of survival of patients on study.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A patient will be eligible for inclusion in this study if all of the following criteria apply: 1. Age ≥ 18 years. 2. Able to give written informed consent. 3. Histologically/cytologically proven malignant melanoma. 4. Unresectable stage III or IV metastatic melanoma with brain metastases. 5. Karnofsky performance score ≥70% (see appendix 1 of trial protocol). 6. RTOG RPA score 1 or 2 (see appendix 6 of trial protocol). 7. Measurable disease as defined by RECIST version 1.1. 8. Life expectancy of at least 12 weeks. 9. Haematological and biochemical indices within the ranges shown below: Haemoglobin (Hb) ≥ 10 g/dL White Blood Count (WBC) ≥ 3 x 109/L Platelet count ≥ 100,000/μL Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L Serum bilirubin ≤ 1.5 x ULN AST or ALT ≤ 2.5 x ULN ALP ≤ 2.5 x ULN Creatinine clearance (Cockcroft-Gault) > 30 ml/min or Serum creatinine ≤ 1.5 x ULN Serum potassium ≥ LLN and < 5.5 mmol/L Serum magnesium ≥ LLN and < 1.23 mmol/L Serum calcium ≥ LLN and < 2.9 mmol/L 10. Adequate cardiac function (NHYA 0-1). 11. QTc <480 msec on screening ECG. 12. The patient is willing and able to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations.
    E.4Principal exclusion criteria
    A patient will not be eligible for the trial if any of the following apply: 1. Any radiotherapy or systemic melanoma therapy within 28 days prior to starting trial treatment, except palliative radiotherapy. 2. Prior whole brain irradiation. 3. CNS melanoma where all detectable disease has been treated by neurosurgery or stereotactic irradiation. 4. Presence of leptomeningeal disease. 5. More than 3 extra-cranial organ sites involved with melanoma. 6. Pregnant or breast-feeding women. Female patients must have a negative urinary or serum pregnancy test or have evidence of post-menopausal status (defined as absence of menstruation for >12 months, bilateral oophrectomy or hysterectomy). 7. Patients (both male and female) of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (as detailed in the study protocol). 8. Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena cava syndrome) within 3 months before study entry (defined as signing of consent form), heart failure (NYHA class 2 or above), presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. 9. Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg, despite treatment). 10. History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE version 4.0 grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded. 11. History of QT prolongation with other medications that required discontinuation of that medication. 12. Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age. 13. Presence of left bundle branch block (LBBB) on screening ECG. 14. Serum calcium, magnesium or potassium below the normal range despite supplementation. 15. Concomitant medications that are potent inducers of CYP3A4 function (see appendix 5 of protocol). 16. Concomitant medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes (see appendix 4 of protocol). If the patient is on any such medications, they need to be stopped at least 14 days prior to day 1 dosing. If they cannot be stopped, the patient is excluded. 17. Ocular malignant melanoma. 18. Another active malignancy within the past five years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin. 19. Any clinically significant and uncontrolled major medical condition(s). 20. Any unresolved toxicity greater than CTCAE version 4.0 grade 1 from previous anti-cancer therapy. 21. Inability to swallow tablets, refractory nausea and vomiting, chronic gastrointestinal disease (eg: inflammatory bowel disease), significant bowel resection, or any other condition that would preclude adequate absorption of vandetanib. 22. Currently active diarrhoea that may affect the ability of the patient to absorb vandetanib or tolerate treatment-induced diarrhoea. 23. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV. 24. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy. 25. Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results. 26. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
    E.5 End points
    E.5.1Primary end point(s)
    Progression free survival in the brain (as assessed by MRI scan and/or clinical symptoms)
    E.5.2Secondary end point(s)
    1. Maintenance of cognitive function 2. PFS in brain at 6 months 3. Overall Survival
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of study.
    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 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 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 concerned10
    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 No
    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
    Protocol defined as when the last patient has completed six months follow up or relapsed.
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    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.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 0
    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 No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state86
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 86
    F.4.2.2In the whole clinical trial 86
    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)
    Not applicable as the intervention of vandetanib/placebo tablets is only for a duration of 21 days, and no further.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-08-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-08-05
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-11-28
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