Pilot Study Investigating the Metabolic Activity and Transcriptional Profiling in Vivo in Tumor Biopsies in Melanoma Patients During Treatment With Pazopanib Alone and in Combination With Paclitaxel

Study Overview
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Brief Summary
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This is an open, monocentric, pilot study to determine the metabolic activity (glucose-uptake) in vivo during monotherapy with pazopanib in comparison to combination therapy with pazopanib plus paclitaxel and to investigate the transcriptional profile of cutaneous melanoma metastasis before and during the therapy (pazopanib vs. pazopanib plus paclitaxel) in subjects with unresectable Stage III or Stage IV melanoma who have not received prior cytotoxic chemotherapy. Primary Objective: Evaluation of metabolic activity in vivo Secondary Objective: Determination of changes in gene expression profiling Evaluation of the antitumor activity of the combination in terms of progression free survival (PFS). Changes in S100 and LDH during therapy at the same time points as FDG-PET/CT (a combined serum measurement of S100 and LDH) Trial with medicinal product

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Pazopanib/Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥ 18 years Diagnosis of histologically or cytologically confirmed melanoma stage III or IV. Fresh tumor tissue must be provided for all subjects for biomarker analysis before (within 14 days prior to treatment start) and during (on day 10 of the pazopanib monotherapy and the last day of the treatment with pazopanib, day 70) treatment with investigational product (asservation in RNAlater, for kryo asservation, and for cell cultures) Assessable metastases (skin or superficial lymph nodes with a minimal diameter 1 cm) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate organ system function Exclusion criteria: Prior malignancy. Central nervous system (CNS) metastases Corrected QT interval (QTc) > 480 msecs using Bazett's formula. History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting; Myocardial infarction; Unstable angina; Coronary artery bypass graft surgery; Symptomatic peripheral vascular disease; Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA). Poorly controlled hypertension History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Presence of uncontrolled infection Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding Evidence of active bleeding or bleeding diathesis Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia. Prior exposure to the study drug pazopanib

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pazopanib/Paclitaxel<br> | Drug: Pazopanib/Paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of metabolic activity in vivo | The primary efficacy objective is to evaluate the metabolic activity in vivo through standardising the uptake value (SUV) in the FDG-PET/CT in comparison of the SUV between baseline, after pazopanib alone (day 10) and after pazopanib plus paclitaxel (day 70). | 84 days ( Baseline, Day 10, Day 70) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of changes in gene expression profiling | Determination of changes in gene expression profiling on exon level in all patients with (sub)-cutaneous or superficial lymph node metastases (of melanoma) during pazopanib and pazopanib plus paclitaxel therapy in comparison to pretreatment profile | 84 days ( Baseline, Day 10, Day 70) | 
| Evaluation of the antitumor activity of the combination in terms of progression free survival (PFS) |  | 112 days | 
| Changes in S100 and LDH during therapy at the same time points as FDG-PET/CT (a combined serum measurement of S100 and LDH) |  | 84 days ( Baseline, Day 10, Day 70) |