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Targeted Therapy Selection Based on Tumor Tissue Kinase Activity Profiles for Patients With Advanced Solid Malignancies, an Exploratory Study

18 Years
Open (Enrolling)
Advanced Solid Tumors, Inoperable, Metastasis

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Trial Information

Targeted Therapy Selection Based on Tumor Tissue Kinase Activity Profiles for Patients With Advanced Solid Malignancies, an Exploratory Study

Specific signalling proteins that are important for tumor growth can be targeted by agents.
These are called targeted agents or targeted treatment. Thus far, it is unclear which
patients will respond to these targeted agents. It is assumed that responses to these agents
depend on specific receptor and protein signalling activities in tumor tissues. The
investigators propose that kinase activity profiling may be a potential clinical diagnostic
tool to predict tumor response to targeted treatment with tyrosine kinase inhibitors.

The investigators will determine ex vivo kinase activity inhibition profiles of tumor tissue
to different targeted agents. Tumor tissue from patients with advanced cancer for whom no
standard treatment is available will be used.

Patients will be treated with the selected targeted agent and the clinical benefit will be

Inclusion Criteria:

- Patients presenting with an advanced (unresectable and/or metastatic) solid
malignancy for whom no standard treatment is available.

- Patients should have received at least one prior standard medical treatment regimen
for their advanced disease.

- Patients with progressive disease within 12 weeks prior to the start of study
medication based on radiological assessment.

- At least one tumor lesion should be assessable for biopsy to perform kinase activity

- Age ≥ 18 years.

- Histological or cytological documentation of cancer is required.

- Patients with at least one measurable lesion. Lesions must be evaluated by CT-scan or
MRI according to Response Evaluation Criteria in Solid Tumors (RECIST).

- WHO performance status 0 - 2

- Life expectancy of at least 12 weeks

- Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:

- Hemoglobin ≥ 5.6 mmol/L

- Absolute neutrophil count (ANC) ≥ 1,500/mm3

- Platelet count ≥ 100x10*9/l

- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) 22 of 59

- ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their

- Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ¡Ý 50 ml/min

- Activated partial thromboplastin time < 1.25 x ULN

- Prothrombin time or INR < 1.25 x ULN

- Patients should be able to swallow oral medication.

- Written informed consent

Exclusion Criteria:

- History of cardiac disease:

- Congestive heart failure >NYHA class 2.

- Active Coronary Artery Disease (myocardial infarction more than 6 months prior
to screening is allowed).

- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin
are permitted).

- Uncontrolled hypertension. Blood pressure must be ≤ 160/95 mmHg at the time of
screening on a stable antihypertensive regimen. Blood pressure must be stable on at
least 3 separate measurements on at least 2 separate days.

- Uncontrolled infections (> grade 2 NCI-CTC version 3.0).

- Subjects with serious non-healing wound, ulcer, or bone fracture.

- History or clinical evidence of central nervous system (CNS) disease, including
primary brain tumor and brain metastases.

- Clinical findings associated, in the judgment of the investigator, with an
unacceptably high tumor biopsy risk

- Pregnant or breast-feeding subjects.

- Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy
during the study or within 4 weeks of the start of study drug.

- Radiotherapy on target lesions during study or within 4 weeks of the start of study
drug. Palliative radiotherapy will be allowed.

- Concomitant use of dexamethasone, anti-convulsants and anti-arrhythmic drugs other
than digoxin or beta blockers.

- Major surgery within 28 days of start of treatment. The surgical wound should be
fully healed prior to the start of study drug. In subjects who experienced wound
healing complications during therapy, treatment should be withheld until the wound is
fully healed.

- Substance abuse, medical, psychological or social conditions that may interfere with
the subject¡-s participation in the study or evaluation of the study results.

- Any condition that is unstable or could jeopardize the safety of the subject and
their compliance in the study.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The clinical benefit rate (CBR) of this therapy selection approach.

Outcome Description:

The clinical benefit rate (CBR) is defined by the number of patients demonstrating either a complete or partial response or stable disease after 12 weeks of treatment.

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Henk Verheul, M.D., PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

VU University Medical Center


Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:




Start Date:

August 2010

Completion Date:

Related Keywords:

  • Advanced Solid Tumors
  • Inoperable
  • Metastasis
  • targeted therapy
  • individualized medicine
  • tyrosine kinase inhibitor
  • kinome profiling
  • Metastasized
  • Neoplasm Metastasis