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Targeted therapy selection based on tumor tissue kinase activity profiles for patients with advanced solid malignancies, an exploratory study

Completed
Conditions
Advanced solid tumors
metastasized or inoperable cancer
10027476
Registration Number
NL-OMON34546
Lead Sponsor
Vrije Universiteit Medisch Centrum
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
43
Inclusion Criteria

Advanced solid malignancy, minimum age 18 years, no standard therapeutic options available, life expectancy of at least 12 weeks, measurable disease with at least one lesion assessable for biopsy.

Exclusion Criteria

Cardiovascular conditions including congestive heartfailure NYHA class >2, recent myocardial infarction or uncontrolled coronary artery disease, uncontrolled hypertension; uncontrolled infections; anticancer treatment during study or within 4 weeks of start of study treatment.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>The primary objective is to determine the clinical benefit rate (CBR) of this<br /><br>therapy selection approach, defined by the number of patients demonstrating<br /><br>either a complete or partial response or stable disease after 12 weeks of<br /><br>treatment. Available phase I data of several registered tyrosine kinase<br /><br>inhibitors have shown CBR*s of approximately 10% in patients with advanced<br /><br>solid malignancies excluding renal cell carcinoma, hepatocellular carcinoma and<br /><br>GIST. Based on these data, we expect to increase CBR by ex vivo analysis and<br /><br>therapy selection to 25%.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>1. To compare progression free survival (PFS) using a kinase inhibitor<br /><br>treatment regimen selected by kinase profiling with the PFS of the most recent<br /><br>treatment regimen on which the patient progressed (i.e., patients are their own<br /><br>controls).<br /><br>2. To determine the relation of Comparative Genomic Hybridization<br /><br>(CGH)-profiles with response to kinase inhibitors.<br /><br>3. To determine the relation of serum and tissue kinome proteomic and activity<br /><br>profiles with response to kinase inhibitors and survival.<br /><br>4. To correlate the frequency and phenotype of immunoregulatory cells in blood<br /><br>and tumor tissue with response to kinase inhibitors.<br /><br>5. To correlate individual pharmacodynamics with response to kinase inhibitors.</p><br>
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