HGG-TCP (High Grade Glioma - Tumor Concentrations of Protein Kinase Inhibitors)

NCT02239952 | Unknown DMC

• 1 other identifier: 2013.465
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine intratumoral concentration of kinase inhibitors upon 2 weeks of treatment in tumor tissue (in the brain) of patients with high-grade gliomas (HGG).

Conditions

Cancer; High-grade Glioma

Outcome Measures

Primary Outcomes (1)

• PKI and active metabolites concentrations in tumor tissue

  PKI concentrations and active metabolites in tumor tissue after approximately two weeks of PKI treatment will be determined.

  2 weeks

Secondary Outcomes (3)

• Correlation of PKI and active metabolites concentrations in tumor.

  2 weeks

• Feasibility of determining the (phospho)proteomic profiles and kinase activity profiles in tumor tissue and CSF.

  2 weeks

• Significant difference of the (phospho)proteomic profiles and kinase activities of tumor tissue in study patients and control group.

  2 weeks

Study Arms (3)

sunitinib

EXPERIMENTAL

Drug: Sunitinib

vandetanib

EXPERIMENTAL

Drug: vandetanib

Erlotinib

EXPERIMENTAL

Drug: Erlotinib

Interventions

Sunitinib DRUG

50 mg once daily, oral use for 14 days

sunitinib

vandetanib DRUG

300 mg, once daily, oral use for 14 days

vandetanib

Erlotinib DRUG

150 mg, once daily, oral use for 14 days

Erlotinib

Eligibility Criteria

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

You may qualify if:

• Patients without a history of brain tumor
• Initial brain MR-scan suggesting a high grade glioma, according to the interpretation of an expert neuroradiologist
• On initial MR-scan a tumor localisation that is deemed resectable without major neurological deficits
• Patients must have a Karnofsky Performance Score ≥ 70%
• Patients must have a RTOG Neurologic Function Status of 0-2
• Patients need to have adequate hematological, renal and hepatic function as assessed by the following laboratory requirements to be conducted within seven days prior to start study treatment: - Hemoglobin \> 7.0 mmol/l - Absolute neutrophil count (ANC) \>1,5 x 10\*9/l - Platelet count \> 100 x 10\*9/l - ALT and AST\< 2.5 x ULN - Alkaline phosphatase \< 4 x ULN - Serum creatinine eGFR \> 50 ml/min
• Patients are 18 years of older
• Male and female patients with reproductive potential must use an approved contraceptive method during and for three months after discontinuation of study treatment
• Patients need to give informed consent
• Patients should be able to swallow oral medication

You may not qualify if:

• Patients receiving prior chemotherapy, radiotherapy or anti-angiogenic therapy
• Use of anti-coagulant therapy
• Use of CYP3A4 enzyme-inducing drugs, other than dexamethasone (including Carbamazepine, Phenytoine, Phenobarbital)
• Initial MR-scan of the brain showing tumor hemorrhage or intracerebral hemorrhage
• Patients with progressive neurological symptoms despite dexamethasone
• Inability to comply with protocol or study procedures
• Pregnancy
• Patients with uncontrolled arterial hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen.
• Patients with a history of cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Patients with evidence or history of bleeding diathesis
• Patients with a history of venous or arterial thrombo-embolic events or hemorrhagic disease during the past six months
• Patients with a history of congestive heart failure (NYHA III, IV)
• Patients with a history of peripheral vascular disease (Fontaine stage III and IV)
• Patients with stroke or myocardial infarction during the past six months
• Patients with a history of a recent peptic ulcer disease (endoscopically-proven gastric ulcer, duodenal ulcer of esophageal ulcer) during the past six months

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, North Holland, 1081 HV, Netherlands

RECRUITING

Related Publications (1)

• van Linde ME, Labots M, Brahm CG, Hovinga KE, De Witt Hamer PC, Honeywell RJ, de Goeij-de Haas R, Henneman AA, Knol JC, Peters GJ, Dekker H, Piersma SR, Pham TV, Vandertop WP, Jimenez CR, Verheul HMW. Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma. Clin Cancer Res. 2022 Apr 14;28(8):1595-1602. doi: 10.1158/1078-0432.CCR-21-1933.

  PMID: 35165100 DERIVED

MeSH Terms

Conditions

Neoplasms; Glioma

Interventions

Sunitinib; vandetanib; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinazolines

Central Study Contacts

M.E. Van Linde, MD

CONTACT

+31 (0)20 4444321; dm-onc@vumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: August 28, 2014
• First Posted: September 15, 2014
• Study Start: November 1, 2014
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

NL (1)