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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
VitrOmics BV
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT01190241
First received: August 26, 2010
Last updated: March 19, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to select targeted treatment based on ex vivo kinase activity inhibition profiles to targeted agents of tumor tissue from patients with advanced cancer for whom no standard treatment is available.


Condition Intervention
Advanced Solid Tumors
Inoperable
Metastasis
Drug: desatinib or sunitinib or erlotinib or everolimus or lapatinib or sorafenib

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Targeted Therapy Selection Based on Tumor Tissue Kinase Activity Profiles for Patients With Advanced Solid Malignancies, an Exploratory Study

Resource links provided by NLM:


Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • The clinical benefit rate (CBR) of this therapy selection approach. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 45
Study Start Date: August 2010
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Targeted treatment
Targeted treatment with desatinib or sunitinib or erlotinib or everolimus or lapatinib or sorafenib
Drug: desatinib or sunitinib or erlotinib or everolimus or lapatinib or sorafenib
The drug will be selected based on ex vivo test on the tumor tissue. The patients will be treated with the selected drug until disease progression.

Detailed Description:

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 determined.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 analysis.
  • 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 cancer)
    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01190241

Locations
Netherlands
Medical Center Alkmaar
Alkmaar, Netherlands, 1815 JD
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
VitrOmics BV
Investigators
Principal Investigator: Henk Verheul, M.D., PhD VU University Medical Center
  More Information

No publications provided

Responsible Party: H.M.W. Verheul, MD, PhD, Professor of Medical Oncology, VU University Medical Center
ClinicalTrials.gov Identifier: NCT01190241     History of Changes
Other Study ID Numbers: 2010/124
Study First Received: August 26, 2010
Last Updated: March 19, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:
targeted therapy
individualized medicine
tyrosine kinase inhibitor
kinome profiling
Metastasized

Additional relevant MeSH terms:
Erlotinib
Everolimus
Lapatinib
Sorafenib
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014