Treatment of patients with metastatic melanoma with Tadalafil

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 12

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.
h)No medical contraindication to biopsy of target lesion.
i)Willingness and ability to give signed written informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

j)Any evidence of brain metastases
k)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).
l)Concurrent medication with nitrates
m)Uncontrolled blood pressure (<90/50mm Hg or uncontrolled hypertone)
n)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
o)Patients who have a history of depression requiring hospitalization
p)Patients with seizure disorders requiring anticonvulsant therapy
q)Concurrent systemic glucocorticoids or any other systemic immunosuppressive therapy
r)History of ischemic neuropathy of the optical nerve (NAION)
s)Brain insult within the last 6 months
t)Anatomic penis deformation or history of priapismus or predisposing illness like sickle cell anemia or hyperglobulinaemia
u)Patients with a history of a curatively treated malignancy must be disease-free and have a survival prognosis that exceeds five years.
v)Unwilling or unable to comply with the requirements of the protocol
w)Pregnant or lactating women
x)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 in female or male patients

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Immune response as assessed by number of CD8+ cells in fresh tumor tissue by FACS;Secondary Objective: - Other immune response parameters as number of CD4+ and CD8+ cells in tumor tissue by IHC and proliferation of CD8+ lymphocytes in peripheral blood mononuclear cells by FACS<br>- Response rate (CR + PR) and Disease control rate (CR + PR +SD) according to irRC and RECIST<br>- Tolerability <br>- Optimal dosing schedule for Tadalafil<br>- Treatment-related side effects <br>- Progression-free survival after 8 weeks of treatment<br>- Quality of life (EORTC-QLQ-C30, SF-12)<br>;Primary end point(s): Immune response as assessed by number of CD8+ cells in fresh tumor tissue by FACS [ Time Frame: The primary endpoint, patient immune response, will be assessed 4 weeks after start of treatment as compared to pre-treatment.] ;Timepoint(s) of evaluation of this end point: after 8 weeks of treatment

Secondary Outcome Measures