Trial document




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  DRKS00004455

Trial Description

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Title

Randomized, double-blind, placebo controlled Phase II study to evaluate the efficacy and safety of Sorafenib treatment in patients with advanced (recurrent, persistent and/or metastasizing) medullary thyroid carcinoma (SUMMIT).

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Trial Acronym

[---]*

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URL of the Trial

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Brief Summary in Lay Language

The aim of this study is to evaluate the effectiveness and safety of the drug sorafenib in patients with medullary thyroid carcinoma (MTC) when administered over multiple treatment cycles. The extent to which sorafenib can inhibit the progress of the disease is of particular importance. Furthermore, the tolerability and the effect of sorafenib on quality of life are examined.

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Brief Summary in Scientific Language

This is a randomized, double-blind, placebo controlled, multicentre, phase II study designed to evaluate the efficacy and safety of Sorafenib versus placebo in subjects with locally advanced, defined as recurrent, persistent and/or metastatising medullary thyroid cancer. 110 subjects will be randomized to receive either Sorafenib or placebo in a blinded fashion.

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Organizational Data

  •   DRKS00004455
  •   2012/10/11
  •   [---]*
  •   yes
  •   Approved
  •   79/12, Ethik-Kommission der Universität Ulm
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Secondary IDs

  •   2011-006250-90 
  •   4038111 
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Health Condition or Problem studied

  •   C73 -  Malignant neoplasm of thyroid gland
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Interventions/Observational Groups

  •   Oral intake of 400 mg Sorafenib (Nexavar) bid (2 x 2 tbl./d) until disease progression or unacceptable toxicity. Afterwards follow-up for overall survival.
  •   Oral intake of Placebo bid (2 x 2 tbl./d) plus best supportive care until documented disease progression. After unblinding subjects will receive Sorafenib 400 mg bid (2 x 2 tbl./d) until further disease progression. Afterwards follow-up for survival.
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Double or multiple blind
  •   patient/subject, therapist/clinician
  •   Placebo
  •   Treatment
  •   Parallel
  •   II
  •   N/A
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Primary Outcome

Progression-free survival (PFS) measured as time from randomization to disease progression or death based on RECIST v1.1 evaluation or based on Tumour marker progress (CEA or calcitonin) in the first section of the study between the sorafenib treated patients and the placebo group (prior to cross-over to sorafenib).

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Secondary Outcome

Secondary endpoints are the comparisons of sorafenib and placebo group (for each tratment period - both after randomisation and after cross-over) with regard to:
• Time To Progression (TTP)
• DCR (CR + PR + SD rate) in first period of the study before cross-over
• Overall Response Rate (ORR = CR rate + PR rate) in first period
• Response duration in first period
• Overall Survival (OS)
• PFS after cross-over (only descriptive analysis)
• TTP after cross-over
• DCR after cross-over
• Overall Response Rate (ORR = CR rate + PR rate) after cross-over
• Safety
• Patient reported outcomes (PROs), defined as health-related quality of life (FACT-G and EQ-5D)

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Countries of Recruitment

  •   Germany
  •   Austria
  •   United Kingdom
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • Medical Center 
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Recruitment

  •   Planned
  •   2012/10/19
  •   110
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

• Histologically confirmed medullary thyroid carcinoma (C-cell thyroid carcinoma)
• Recurrent or persistent local disease and/or distant metastases not suitable for local curative treatment (surgery or radiation therapy) assessed by Investigator
• No more than one prior line of systemic therapy (including no more than 1 prior line with a targeted drug, e.g. kinase inhibitor)
• Best available supportive care to control (endocrine) symptoms according to current standards established for at least 8 weeks before study entry
• At least one defined lesion in CT or MRI evaluable for RECIST (v1.1), no older than 42 days from planned treatment start, or at least one defined lesion in CT or MRI not evaluable by RECIST in combination with elevated tumour markers with minimum initial levels of 150 pg/ml for calcitonin or 5 x UILN for CEA (e.g., in case of bone metastases)
• Progression within previous 12 months (according to RECIST 1.1 criteria or tumour marker progression (calcitonin or CEA referred to normal Reference Ranges from Site Lab) can be used as a basis for the assessment of disease progression); tumour marker doubling time must be no longer than 12 months (30) and a minimum initial level of 150 pg/ml for calcitonin or 5 x UILN for CEA, respectively, need to be present. The tumour marker doubling time should be estimated using the calculator at the ATA-website: http://www.thyroid.org/professionals/calculators/CDTC.php
• Hb > 8g/dl, WBC >3.000 cells/mm³ (ANC > 1.500 cells/mm³), platelets > 100.000 cells/mm³, bilirubin < 2mg/dl, Alanine aminotransaminase (ALT) and Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (referred to normal Reference Ranges from Site Lab)
• Performance status: WHO ≤ 2; Karnofsky index ≥ 50%
• Patients should have sufficient renal function, as determined by serum creatinine <1.5 mg/dl and CrCL > 30ml/min
• PT-INR and PTT < 1.5 x upper limit of normal (referred to normal Reference Ranges from Site Lab) [Patients who are being therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists]
• No acute infections at the time of therapy initiation
• Staging studies (MRT or CT and Calcitonin or CEA) completed within four weeks of protocol randomisation
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
• Women and men of childbearing potential must agree to use adequate contraception (barrier method of birth control)
• Patient is able to understand the study procedures, voluntarily agrees to participate in the study and has given a signed and dated written informed consent prior to study participation.

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Exclusion Criteria

• Unresolved toxicity (i.e. neurotoxicity) attributed to any prior therapy higher than NCI-CTCAE (version 4) Grade 2 (excluding cases of alopecia)
• Patients with history of allergic or hypersensitivity reaction to study drug or placebo or their excipients or with a history of allergic reactions attributed to compounds with similar composition to any of the study drug or placebo.
• Current participation in another investigational trial
• Patients with significant cardiovascular disease, such as myocardial infarction < 6 months, unstable coronary artery disease (anginal symptoms at rest), new-onset angina within 3 months before randomization, or chronic heart failure (New York Heart Association grade III or IV)
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy other than beta-blockers or digoxin
• Congenital long QTc syndrome, history of drug induced QTc prolongation, or QTc interval unmeasurable or more than 450 ms
• Abnormal serum electrolytes such as potassium, magnesium and calcium
• Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal management
• Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization
• Non-healing wound, ulcer, or bone fracture
• Evidence or history of bleeding diathesis or coagulopathy disorder
• Hemorrhage/bleeding event ≥ Grade 3 within 3 months prior to first dose of study drug
• Thrombotic or embolic events including transient ischemic attacks within the past 6 months
• Subjects with symptomatic brain metastases or Subjects with brain metastases under corticosteroid treatment. Previous or concurrent cancer that is distinct in primary site or histology from thyroid cancer within 5 years prior to randomization EXCEPT cervical cancer in situ, treated basal cell carcinoma and superficial bladder tumours [Ta (Non invasive tumour), Tis (Carcinoma in situ) and T1 (Tumour invades lamina propria)]
• Pregnant or breast-feeding patients
• Patients with uncontrolled infections

• Known human immunodeficiency virus (HIV) infection or infection with hepatitis B or C
• Immunosuppression
• Subjects with seizure disorder requiring medication (such as steroids or anti¬epileptics)
• Subjects undergoing renal dialysis
• Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results
• Any malabsorption condition
• Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study

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Addresses

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    • EANM Forschungs GmbH/ EANM Research Ltd.
    • Ms.  M.A.  Andrea  Bauer 
    • Hollandstraße 14 / Mezzanine
    • A-1020  Wien
    • Austria
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    •   +43 1212 8030
    •   +43 2121 80309
    •   earl at eanm.org
    •   [---]*
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    • Universitätsklinikum Ulm Klinik für Nuklearmedizin
    • Mr.  Prof. Dr. med.  Markus  Luster 
    • Albert-Einstein-Allee 23
    • D-89081  Ulm
    • Germany
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    • ABX-CRO GmbH
    • Mr.  Dipl.-Med.  Ingo  Weigmann 
    • Blasewitzer Straße 78 - 80
    • D-01307  Dresden
    • Germany
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Sources of Monetary or Material Support

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    • EANM Forschungs GmbH / EANM Research Ltd.
    • Ms.  M.A.  Andrea  Bauer 
    • Hollandstraße 14 / Mezzanine
    • A-1020  Wien
    • Austria
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    •   +43 1212 8030
    •   +43 2121 80309
    •   earl at eanm.org
    •   [---]*
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Status

  •   Recruiting stopped after recruiting started
  •   2013/04/22
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.