Trial document




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  DRKS00000689

Trial Description

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Title

Open unicenter phase I trial of a combination therapy of temsirolimus and irinotecan in patients with
glioblastoma or brain metastases of solid tumors

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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 the definition of the well tolerated dose of Temsirolimus in combination with Irinotecan. Overall patients who get special drugs, which are known as CYP3A4 inducers will get a higher dose than patients without these drugs. The first patients got a low dose of Temsirolimus. If this dose is well tolerated the dose will be increased for the next patients and so on.
At the start of trial the patient will get Irinotecan (infusion) at first. If this is well tolerated the patient will get also Temsirolimus and Irinotecan in the next week. Temsirolimus will be given weekly (Infusion). Irinotecan will be given in week 0 and 1, 3 and 4 and 6 and 7.
The trial duration is 50 days. If the investigator and the patient decide to continue the combined therapy with Temsirolimus and Irinotecan after the participation in the trial in case of good efficacy and tolerance, the further application of the drugs is a case of off label use. Such therapy continuation will not be covered by the insurance policy related to the trial. This matter must be clearly communicated to the patient and a separate and updated consent must be obtained.

The maximum tolerated dose was not achieved. Therefore 2 additional dose groups were entered in this trial. This amendment was approved by IEC and authorities at 14May2014

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Brief Summary in Scientific Language

The aim of this study is the definition of the maximum tolerated dose (MTD) of Temsirolimus in combination
with Irinotecan by means of dose-limiting toxicities.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00000689
  •   2011/01/19
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  •   yes
  •   Approved
  •   10-4494, Ethik-Kommission der Medizinischen Fakultät der Universität Duisburg-Essen
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Secondary IDs

  •   2010-021899-28 
  •   4036628 
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Health Condition or Problem studied

  •   C71 -  Malignant neoplasm of brain
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Interventions/Observational Groups

  •   patients with CYP3A4 inducers: 170 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 30 mg Temsirolimus -Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
  •   patients with CYP3A4 inducers: 170 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 40 mg Temsirolimus-Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
  •   patients with CYP3A4 inducers: 170 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 50 mg Temsirolimus-Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
  •   patients without CYP3A4 inducers: 85 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 15 mg Temsirolimus-Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
  •   patients without CYP3A4 inducers: 85 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 20 mg Temsirolimus-Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
  •   patients without CYP3A4 inducers: 85 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 25 mg Temsirolimus-Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
  •   patients without CYP3A4 inducers: 85 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 50 mg Temsirolimus-Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
  •   patients without CYP3A4 inducers: 85 mg/m² Irinotecan-Infusion Day 1, 8, 22, 29, 43, 50 + 75 mg Temsirolimus-Infusion start at day 8 on a weekly basis (3 to 6 patients over 50 days)
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Characteristics

  •   Interventional
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  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Treatment
  •   Other
  •   I
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Primary Outcome

Determining the maximum tolerable dose (MTD) of Irinotecan and Temsirolimus at combined administration by observing dose-limiting toxicities (DLT).

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Secondary Outcome

- analysis of the pharmakokinetics and pharmakodynamics of temsirolimus and
irinotecan under combined administration on day 1, 8, 15, 22, 29, 36, 43 and 50
- time to progression on day 43
- Overall Survival (OS)
- ECOG at screening and on day 1, 8, 15, 22, 29, 36, 43 and 50

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Actual
  •   2011/04/04
  •   48
  •   Monocenter trial
  •   National
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Inclusion Criteria

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

- Recurrence or progression of a histologically confirmed malignant glioblastoma WHO-grade IV or anaplastic astrocytoma WHO-grade III without pathological safeguard fulfilling magnetic resonance imaging criteria of a glioblastoma
- Progressive singular cerebral metastasis of a solid tumor without the option of surgery or irradiation or multiple progressive cerebral metastases after standard irradiation therapy
- Remission of reversible adverse reactions of previous systemic therapy
- No administration or steady dose of glucocorticoids within at least the last week before the first cerebral MRI
- One line of therapy of the recurrent or progressive disease at most, which has to be completed at least 4 weeks, in case of first line administration of nitrosourea 6 weeks, before inclusion
- Patient consents to stay in hospital for the first combined administration of Temsirolimus and Irinotecan
- Age ≥ 18 years
- ECOG Performance Status 0-2
- Estimated life expectancy of at least 3 months
- At least one measurable lesion on MRI according to RECIST
- Patient must avoid drinking of grapefruit juice during participation in the trial
- Signed informed consent
- A previous irradiation therapy must be terminated at least 12 weeks before inclusion

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Exclusion Criteria

- A second malignoma requiring irradiation or chemotherapy
- Scheduled surgery within the timeframe of trial conduction
- Infratentorial localisation of the tumor
- Cardiac arrhythmia requiring anti-arrhythmic therapy
- Myocardial infarction < 6 months before start of therapy
- Symptomatic coronary disease
- Heart failure NYHA class III or IV or LVEF < 50% on echocardiogram or heart volume scintigram
- Angina pectoris
- Diarrhea at the start of therapy
- Neutrophil granulocytes < 1500/μl
- Haemoglobin < 10 g/dl
- Thrombocytes < 100 000/μl
- Serum creatinine > 1,5 times the laboratory´s upper limit value
- Bilirubin > 1.5 mg/dl
- Alkaline phosphatase > 2.5 times the laboratory´s upper limit value
- GOT / GPT > 2.5 times the laboratory´s upper limit value
- Hereditary fructose intolerance
- Inflammatory bowel disease
- Ileus
- Uncontrolled diabetes
- Hypersensitivity to Irinotecan or Temsirolimus
- Serious internistic or neurological disease with poor prognosis (e.g. HIV-infection)
- Diseases that are associated with repeated vomitting and thus interfere with the oral intake of medication
- Psychological, domestic, sociological or geographical circumstances which could interfere significantly with compliance in regard to attending follow-up visits
- Concurrent participation in other therapeutic trials
- Pregnancy / Breastfeeding
- patient did not practice safe contraception, only women of childbearing potential (intrauterine device plus condom, spermicide plus condom or intrauterine device plus spermicide)
- Men, whose female cohabitant of childbearing potential does not practice safe contraception (in this case hormonal contraception is regarded as safe)
- HIV-Infection
- Active drug abuse
- Chronic alcohol abuse

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Addresses

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    • Universitätsklinikum Essen
    • Hufelandstraße 55
    • 45147  Essen
    • Germany
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    • Universitätsklinikum Essen Innere Klinik (Tumorforschung)
    • Mr.  Dr.  Jörg  Hense 
    • Hufelandstraße 55
    • 45122  Essen
    • Germany
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    • Universitätsklinikum Essen Innere Klinik (Tumorforschung)
    • Ms.  Dr.  Heike  Richly 
    • Hufelandstraße 55
    • 45122  Essen
    • Germany
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    • Universitätsklinikum Essen Innere Klinik (Tumorforschung)
    • Ms.  Dr.  Heike  Richly 
    • Hufelandstraße 55
    • 45122  Essen
    • Germany
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    • Universitätsklinikum Essen Innere Klinik (Tumorforschung)
    • Mr.  Dr.  Jörg  Hense 
    • Hufelandstraße 55
    • 45122  Essen
    • Germany
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Sources of Monetary or Material Support

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    • Wyeth Pharma GmbH
    • 48159  Münster
    • Germany
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Status

  •   Recruiting complete, follow-up complete
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  •   2015/05/26
  •   27
  •   27
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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.