Trial document




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  DRKS00003495

Trial Description

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Title

Treatment of patients with metastatic melanoma (AJCC stage IV or III unresectable) with the PDE-inhibitor Tadalafil:
A Pilot Trial for “Proof of Principle”

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Trial Acronym

TaMe

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URL of the Trial

[---]*

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Brief Summary in Lay Language

In this pilot trial with a maximum of 12 participating patients with an inoperable or distant metastasized melanoma it will be investigated if Tadalafil (Cialis®) which is approved for erectile dysfunciton and lung hypertension can improve the clinical course of the disease. Therefore it will be tested if immune cells go into metastases of the melanoma which could be seen in a melanoma mouse model. This led to a pronounced increase in survival of these mice.
In this trial patients can be treated who had at least one pretreatment for their metastasized melanom and have reachable metastases for operation, e.g. skin or lymph nodes.

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Brief Summary in Scientific Language

The study is an open label, monocenter phase IIa clinical trial which is designed as a pilot project in order to establish the biological effect, optimal biological dose, efficacy and tolerability of Cialisâ as palliative treatment of metastatic melanoma. Patients will be treated subsequently in cohorts characterized by different doses (40mg - 20mg – 10mg – 5mg) to analyze dosage dependent effects. Dose deescalation is performed in order to determine dose levels for thresholds of efficacy, whereas previous studies with Tadalafil showed that dosages up to 40mg per day are tolerable.

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Organizational Data

  •   DRKS00003495
  •   2012/01/27
  •   [---]*
  •   yes
  •   Approved
  •   AFmo-417/2011, Ethik-Kommission I der Medizinischen Fakultät Heidelberg
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Secondary IDs

  •   2011-003273-28 
  •   4037650 
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Health Condition or Problem studied

  •   melanoma stage III unresectable and stage IV
  •   C43 -  Malignant melanoma of skin
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Interventions/Observational Groups

  •   one-armed trial with 3 patients each in 4 cohorts with descending doses of 40mg, 20mg, 10mg and 5mg Tadalafil orally for 2 months
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   IIa
  •   Yes
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Primary Outcome

Immune response as assessed by number of CD8+ cells in fresh tumor tissue by Flow cytometric analysis (FACS) at 4 weeks after beginn of treatment

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Secondary Outcome

- Other immune response parameters as number of CD4+ and CD8+ cells in tumor tissue by immunehistochemistry and proliferation of CD8+ lymphocytes in peripheral blood mononuclear cells by flow cytometry (FACS) 4 weeks after begin of treatment
- Response rate (CR + PR) and Disease control rate (CR + PR +SD) according to immune related response criteria (irRC) and RECIST 8 weeks after beginn of treatment
- Tolerability
- Optimal dosing schedule for Tadalafil
- Treatment-related side effects
- Progression-free survival after 8 weeks of treatment
- Quality of life (questionnaires: EORTC-QLQ-C30, SF-12) every 4 weeks

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2012/03/05
  •   12
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   75   Years
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Additional Inclusion Criteria

a) Histologically proven metastatic melanoma
b) Clinical stage IV or III unresectable (AJCC 2010)
c) ≥ 18 to 75 years of age
d) Presence of cutaneous or accessible lymph node metastases (tumor biopsies)
e) Measurable disease (at least one lesion that can be accurately measured in two perpendicular diameters, with at least one diameter ≥ 5 mm and the other dimension ≥ 5 mm assessed by ultrasound)
f) ECOG performance status of 0-2
g) At least one prior treatment for metastatic disease, including established treatments like Ipilimumab.
h) No medical contraindication to biopsy of target lesion.
i) Willingness and ability to understand the informed consent and the quality of life questionnaires and to give signed written informed consent.
j) Women of childbearing potential must agree to use effective contraception during the study.

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Exclusion Criteria

a) Any evidence of brain metastases
b) Patients with severe cardiac disease (e.g. NYHA Functional Class II, III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia requiring ongoing treatment, unstable angina pectoris, sinusbradycardia).
c) Concurrent medication with nitrates, alpha-Blockers e.g. Doxazosin or other interacting medications (CYP3A4 inhibitors e.g. Ketoconazole, Erythromycin, Clarithromycin, Intraconazol and grape fruit juice, CYP3A4 inductors e.g. Rifampicin, Phenobarbital, Phenytoin and Carbamazepin)
d) Uncontrolled blood pressure (<90/50mm Hg or uncontrolled hypertone)
e) laboratory data (to be obtained within 4 weeks of initiation):
Platelets < 75,000/mm³
Calculated Creatinine Clearance (CRCL) < 60 ml/min
ALAT or ASAT > 2 x ULN
Total serum bilirubin > 1.5 mg/dl
f) Patients who have a history of depression requiring hospitalization
g) Patients with seizure disorders requiring anticonvulsant therapy
h) Concurrent systemic glucocorticoids or any other systemic immunosuppressive therapy
i) History of ischemic neuropathy of the optical nerve (NAION)
j) Brain insult within the last 6 months
k) Anatomic penis deformation or history of priapismus or predisposing illness like sickle cell anemia or hyperglobulinaemia
l) Patients with a history of a curatively treated malignancy must be disease-free and have a survival prognosis that exceeds five years.
m) Concurrent treatment with other anti-cancer therapy or parallel participation in another therapeutic trial
n) Known hypersensitivity reaction to Tadalafil or other ingredients of Cialis®.
o) Unwilling or unable to comply with the requirements of the protocol
p) Pregnant or lactating women
q) Unwillingness or inability to employ an effective barrier method of birth control throughout the study and for up to 3 months after end of treatment

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Addresses

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    • Universitätsklinikum Heidelberg
    • Im Neuenheimer Feld 672
    • 69120  Heidelberg
    • Germany
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    • Hautklinik und Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg
    • Ms.  Dr. med.  Jessica  Hassel 
    • Im Neuenheimer Feld 460
    • 69120  Heidelberg
    • Germany
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    • Hautklinik und Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg
    • Ms.  Silvia  Koerner 
    • Im Neuenheimer Feld 460
    • 69120  Heidelberg
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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    • Universitätsklinikum Heidelberg
    • Im Neuenheimer Feld 672
    • 69120  Heidelberg
    • Germany
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Status

  •   Recruiting planned
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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.