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    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7292   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:2004-001356-37
    Sponsor's Protocol Code Number:NSGO-CC-0304
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-08-23
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2004-001356-37
    A.3Full title of the trial
    Phase I-II-III studies of Cisplatin and Combretastatin (CA4P) in recurrent or advanced servical cancer
    A.4.1Sponsor's protocol code numberNSGO-CC-0304
    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 SponsorNordic Society for Gynecological Cancer
    B.1.3.4CountryDenmark
    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 Information not present in EudraCT
    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 nameCombretastatin
    D.3.2Product code CA4P
    D.3.4Pharmaceutical form Powder for infusion*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeCA4P
    D.3.9.3Other descriptive nameCombretastatin
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number36 to 72
    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 No
    D.3.11.3.2Gene therapy medical product No
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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.IMP: 2
    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 Information not present in EudraCT
    D.2.1.1.1Trade name Cisplatin, Platinol
    D.2.1.1.2Name of the Marketing Authorisation holderCisplatin
    D.2.1.2Country which granted the Marketing AuthorisationDenmark
    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 nameCisplatin
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive nameCisplatin
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.3Other descriptive nameCisplatin
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 No
    D.3.11.3.2Gene therapy medical product No
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic or recurrent cervical cancer
    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 determine toxicity, antitumor efficacy and outcome of weekly Cisplatin combined with the antivascular targeting agent Combretastatin in patients with advanced or recurrent cervical cancer considered incurable by standard treatment.
    E.2.2Secondary objectives of the trial
    The primary objective (Phase I) is to establish the maximally tolerated dose (MTD) of Combretastatin combined with weekly Cisplatin in patients with advanced cervical cancer. The secondary objective (Phase II) is to compare the anticancer activity of combined weekly Cisplatin (40 mg/m2) and Combretastatin with standard chemotherapy (Cisplatin 75 mg/m2 every third week). This will be done in a randomized Phase II study. Provided that the experimental arm show sufficient activity in Phase II, the tertiary objective (Phase III) will be to evaluate whether weekly Cisplatin and Combretastatin is superior to standard every third week Cisplatin in terms of survival and health related quality of life (HRQoL).
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    a) Primary advanced (stage IVB), persistent or recurrent cancer of the uterine cervix considered incurable by surgery, radiotherapy and or chemotherapy.
    b) Histological verified squamous carcinoma, adenocarcinoma or adeno-squamous carcinoma
    c) Performance status (WHO) 0 or 1.
    d) Life expectancy > 12 weeks.
    e) Age > 18 years and < 75 years.
    f) For Phase I, a treatment free interval of at least 2 month from previous radiotherapy, chemotherapy or radio-chemotherapy is required.
    g) For Phase II, at least one measurable lesion (RECIST) outside previously irradiated area with clinical evidence of progression within 6 weeks prior to treatment is required. Progressing lesions localized only to previous irradiated volume is allowed in Phase III.
    h) For Phase II-III, prior chemotherapy or radio-chemotherapy is allowed provided that a treatment free interval of at least 6 month is at hand. Previous radiotherapy more than 3 month ago is allowed.
    i) For Phase II-III, patients progressing directly during previous chemotherapy or radio-chemotherapy are ineligible.
    j) Acceptable bone marrow function (leukocytes ³ 3.0x109/L and platelet count 100x109/L).
    k) ECG without evidence of prior myocardial infarction (e.g., significant Q waves), QTc > 450 msec. or other clinically significant abnormalities.
    l) Sufficient kidney function with calculated (Cockroft-Gault) GFR > 50 ml/min and no uncontrolled hypokalemia and/or hypomagnesemia.
    m) Acceptable liver function with bilirubin < 30 μmol/l.
    m) Patients with childbearing potential must have a negative pregnancy test and should use an effective method of contraception (hormonal anticonception or intrauterine device).
    n) Written informed consent according to ICH/EU GCP guidelines and regional and national law.
    E.4Principal exclusion criteria
    a) No combination of protocol treatment with attempts of curative surgery or radiotherapy.
    b) No previous inclusion in the protocol.
    c) No other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin.
    d) No CNS metastases.
    e) No major surgery within 4 weeks.
    f) No concomitant administration of other antineoplastic agents.
    g) No palliative radiotherapy unless at least one measurable lesion is left unirradiated.
    h) No history of angina (stable or more severe, even if controlled with medications), myocardial infarction, chronic heart failure, non-controlled atrial arrhythmias or clinically significant arrhythmias including conduction abnormality, nodal junctional arrhythmias and dysrhythmias, sinus bradycardia or tachycardia, supraventricular arrhythmias, atrial fibrillation or flutter, syncope or vasovagal episodes.
    i) Patients taking any drug(s) known to prolong the QTc interval, which cannot be interrupted for at least four days during each 7-day treatment cycle or patients with conditions associated with QTc prolongation cannot be included
    j) No uncontrolled hypertension (defined as blood pressure consistently greater than 150/100 mmHg irrespective of medication).
    k) No symptomatic peripheral vascular disease or cerebrovascular disease.
    l) No grade 2 (CTC v.3.0) or greater pre-existing peripheral neuropathy (motor or sensory);
    m) No psychiatric disorders or other conditions rendering patients incapable of complying with the requirements of the protocol.
    n) No active infection or other severe medical condition endangering treatment delivery.
    o) Patients, for whom regular follow-up attendance is impractical, are not eligible.
    E.5 End points
    E.5.1Primary end point(s)
    Phase I
    As toxicity is the primary endpoint a treatment free interval of at least 2 month from previous chemotherapy, radiotherapy or radio-chemotherapy is required to ensure that toxicity from previous treatment does not interfere with toxicity induced by Cisplatin and Combretastatin.

    Successive cohorts of 6 patients will be included in the trial at each dose level. The patients will be replaced, if they go off study before having received the first complete cycle (3 weekly infusions) of chemotherapy for any reason except toxicity. The time window for registration of dose limiting toxicity (DLT) is the first cycle of treatment (3 weekly infusions). Each cohort will be observed for a total of 6 weeks before a new dose level can be opened. However, any new toxicity encountered during subsequent treatment cycles should not be regarded as DLT.

    Three dose levels will be investigated. If 1 of 3 patients at a given dose level encounters dose limiting toxicity (DLT) the study proceeds at the same dose level for a total of 6 patients. As soon as more than 2 patients encounters DLT this dose level is declared as maximally tolerated dose (MTD). The dose level immediately below MTD will be declared as the recommended Phase 2 dose (RP2D). Additional dose levels with increments of 9 mg/m2 (free acid dose) of Combretastatin per dose level may be opened if MTD is not reached at the initial three dose levels.

    Phase-II
    Phase II involves an open labeled, stratified and one-to-one randomization between every third week Cisplatin 75 mg/m2 and weekly Cisplatin 40 mg/m2 combined with Combretastatin given at the RP2D dose level. As tumor growth delay rather than tumor regression is anticipated with Combretastatin, the primary endpoint is absence of early progression, defined as absence of objective progression at 6 weeks and confirmed at 12 weeks. Disease status will be assessed according to the "RECIST" criteria. Duration of complete response, partial response and stable disease will also be assessed. The Simon design for randomized Phase II trials will be applied with a total of 36 eligible patients registered in each arm. To guard against ineligible or unevaluable cases, the target accrual is set to 80 patients.

    Phase-III
    Provided that the objectives for Phase II are reached the study may be continued directly as a Phase III study.

    As survival is the primary endpoint and progression free survival and health related quality of life are the secondary endpoints, patients with no lesions outside previously irradiated volume are eligible. Patients previously treated with chemotherapy administered either as radiosensitizer or for disseminated are also eligible provided a treatment free interval of at least 6 month is at hand.

    Patients will be randomized between every third week Cisplatin 75 mg/m2 and weekly Cisplatin 40 mg/m2 combined with Combretastatin given at the RP2D level.

    The exact number of required patients is unknown at present and will be calculated according to the results obtained in Phase II. However, a total of at least 400 patients are most likely required to determine a clinical relevant prolongation of median survival with sufficient power.

    The primary endpoint will be overall survival with progression free survival and HRQoL as secondary endpoints. Patient assessment of HRQoL will be obtained by use of a standardized and validated questionnaire (EORTC QoL-C30). The HRQoL data will be evaluated according to the scoring manual of the EORTC Quality of Life Study Group.
    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 Yes
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Combination with chemotherapy
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 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) Yes
    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.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    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.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state100
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 320
    F.4.2.2In the whole clinical trial 420
    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 Decision2004-08-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2004-09-10
    P. End of Trial
    P.End of Trial StatusCompleted
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