Temozolomide and Radiation Therapy With or Without Vatalanib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT00128700 | Completed Phase 1

• 4 other identifiers: EORTC-26041-22041EORTC-26041EORTC-22041EUDRACT-2004-003896-35
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 5

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Vatalanib may stop the growth of tumor cells by blocking blood flow to the tumor. Giving temozolomide and radiation therapy together with vatalanib may kill more tumor cells. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of vatalanib when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity and maximum tolerated dose of vatalanib as determined by CTCAE v3.0 during phase I

• Progression-free survival at 6 months during phase II

Secondary Outcomes (3)

• Severe toxic events as assessed by CTCAE v3.0 at weeks 3 and 6 (concomitant treatment), weeks 2 and 4 after radiotherapy, before each course of adjuvant treatment, monthly during maintenance treatment, and every 3 months during follow-up in phase II

• Overall survival at 1 year during phase II

• Correlation of angiogenesis and hypoxia markers expression and O-6-methylguanine DNA methyltransferase (MGMT) methylation status with clinical outcome during phase II

Interventions

temozolomide DRUG

vatalanib DRUG

adjuvant therapy PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed glioblastoma multiforme * Newly diagnosed disease * Deemed to be amenable to concurrent and adjuvant temozolomide treatment by the principal investigator PATIENT CHARACTERISTICS: Age * 18 to 69 Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin \< 1.5 times upper limit of normal (ULN) * Alkaline phosphatase \< 2.5 times ULN * ALT and AST \< 2.5 times ULN Renal * Creatinine ≤ 1.7 mg/dL Cardiovascular * Cardiac function clinically normal * 12-lead ECG normal * No ischemic heart disease within the past 6 months * No uncontrolled cardiac arrhythmia * No uncontrolled hypertension * No history of stroke * No history of congenital long QT syndrome * QTc interval ≤ 450 msec for males or ≤ 470 msec for females by 12-lead ECG Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other malignancy except adequately treated basal cell or squamous cell skin cancer or cone biopsied carcinoma in situ of the cervix * No active uncontrolled infection * No other unstable systemic disease * No psychological, familial, sociological, or geographical condition that would preclude study compliance or follow-up schedule PRIOR CONCURRENT THERAPY: Biologic therapy * No prior anti-vascular endothelial growth factor therapy Chemotherapy * No prior chemotherapy Endocrine therapy * Concurrent corticosteroids allowed provided the patient is on stable or decreasing doses for ≥ 2 weeks before study entry Radiotherapy * No prior radiotherapy Surgery * More than 8 days, but \< 6 weeks, since prior surgery or biopsy Other * No prior randomization on this study * No concurrent warfarin, warfarin-derived drugs, or similar anticoagulants * No other concurrent anticancer therapy * No other concurrent investigational agents * No concurrent enzyme inducing antiepileptic drugs, including any of the following: * Carbamazepine * Fosphenytoin * Oxcarbazepine * Phenobarbital * Phenytoin * Primidone * No concurrent grapefruit or grapefruit juice

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (5)

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Klinikum der Universitaet Regensburg

Regensburg, D-93053, Germany

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Daniel Den Hoed Cancer Center at Erasmus Medical Center

Rotterdam, 3075 EA, Netherlands

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Related Publications (2)

• Brandes AA, Stupp R, Hau P, Lacombe D, Gorlia T, Tosoni A, Mirimanoff RO, Kros JM, van den Bent MJ. EORTC study 26041-22041: phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma. Eur J Cancer. 2010 Jan;46(2):348-54. doi: 10.1016/j.ejca.2009.10.029. Epub 2009 Nov 27.

  PMID: 19945857 RESULT

• Brandes AA, Stupp R, Hau P, et al.: EORTC Study 26041-22041: phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with or without PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma: results of a phase I trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-2026, 2007.

  RESULT

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Temozolomide; vatalanib; Chemotherapy, Adjuvant; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Alba A. Brandes, MD

  Azienda Ospedaliera di Padova

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2005
• First Posted: August 10, 2005
• Study Start: June 1, 2005
• Primary Completion: November 1, 2007
• Last Updated: September 24, 2012

Record last verified: 2012-09

Locations

BE (1); DE (1); IT (1); NL (1); CH (1)