Previously treated metastatic melanoma in stage IV or III unresectable MedDRA version: 14.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Cialis
Product Name: Cialis
Pharmaceutical Form: Film-coated tablet
Trade Name: Cialis
Product Name: Cialis
Pharmaceutical Form: Film-coated tablet
Trade Name: Cialis
Product Name: Ciali
Sponsors
Ruprecht-Karls-University Heidelberg, Med Faculty represented by Universitätsklinikum Heidelberg and its Commercial D
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 ( 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 - Response rate (CR + PR) and Disease control rate (CR + PR +SD) according to irRC and RECIST - Tolerability - Optimal dosing schedule for Tadalafil - Treatment-related side effects - Progression-free survival after 8 weeks of treatment - Quality of life (EORTC-QLQ-C30, SF-12) ;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
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 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 [ Time Frame: The primary endpoint, patient immune response, will be assessed by several parameters quantifying the presence and function of MDSC and T cell populations 4 weeks after start of treatment as compared to pre-treatment.] - Response rate (CR + PR) and Disease control rate (CR + PR +SD) according to irRC and RECIST - Tolerability - Optimal dosing schedule for tadalafil [ Time Frame: Analysis will be performed on patient tumor specimens obtained 4 weeks after begin of treatment ] - Treatment-related side effects [ Time Frame: Side effects will be assessed via questionnaire at Day 5 and Day 20 of treatment ] [ Designated as safety issue: Yes ] - Progression-free survival at 8 weeks of treatment [Time Frame: From the date of initiation of study treatment to the date of documented disease progression or death from any cause, whichever is earlier.] - Quality of life (EORTC-QLQ-C30, SF-12) ;Timepoint(s) of evaluation of this end point: after 8 weeks of treatment | — |
Countries
Germany
Contacts
Public ContactSkin Cancer Center
Department of Dermatology, Universtiy Hospital Heidelberg
Outcome results
None listed