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

NCT01190241 | Terminated

• 1 other identifier: 2010/124
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Advanced Solid Tumors; Inoperable; Metastasis

Keywords

targeted therapy; individualized medicine; tyrosine kinase inhibitor; kinome profiling; Metastasized

Outcome Measures

Primary Outcomes (1)

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

  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.

  12 weeks

Study Arms (1)

Targeted treatment

EXPERIMENTAL

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

Interventions

desatinib or sunitinib or erlotinib or everolimus or lapatinib or sorafenib DRUG

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.

Targeted treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• VitrOmics BV: collaborator

Study Sites (2)

Medical Center Alkmaar

Alkmaar, 1815 JD, Netherlands

Location

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (1)

• Labots M, Van der Mijn JC, Dekker H, Ruijter R, Pham TV, Van der Vliet HJ, Van der Hoeven JJM, Meijer GA, Verheul HMW. Selection of Protein Kinase Inhibitors Based on Tumor Tissue Kinase Activity Profiles in Patients with Refractory Solid Malignancies: An Interventional Molecular Profiling Study. Oncologist. 2018 Oct;23(10):1135-e118. doi: 10.1634/theoncologist.2018-0263. Epub 2018 Jul 17.

  PMID: 30018133 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Sunitinib; Erlotinib Hydrochloride; Everolimus; Lapatinib; Sorafenib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines; Sirolimus; Macrolides; Lactones; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Henk Verheul, M.D., PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: medical oncologist

Study Record Dates

• First Submitted: August 26, 2010
• First Posted: August 27, 2010
• Study Start: August 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: November 20, 2020

Record last verified: 2020-11

Locations

NL (2)