Bevacizumab in Recurrent Grade II and III Glioma (TAVAREC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01164189
First received: July 15, 2010
Last updated: November 4, 2013
Last verified: November 2013
  Purpose

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. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether temozolomide is more effective when given with or without bevacizumab in treating patients with recurrent glioma.

PURPOSE: This randomized clinical trial is studying how well temozolomide works with or without bevacizumab in treating patients with recurrent glioma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Biological: Bevacizumab
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial Assessing the Significance of Bevacizumab in Recurrent Grade II and Grade III Gliomas - The TAVAREC Trial

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Probability of survival at 1 year [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate and duration of response [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival and survival at 24 months [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]
  • Clinical/neurological deterioration-free survival [ Designated as safety issue: No ]
  • Steroid use [ Designated as safety issue: No ]
  • Quality of life of patients and caregivers/relatives [ Designated as safety issue: No ]
  • Cognitive deterioration [ Designated as safety issue: No ]

Estimated Enrollment: 144
Study Start Date: February 2011
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Temozolomide Drug: Temozolomide
Temozolomide (250, 100, 20 and 5 mg caps) will be administered orally on day 1-5, 150-200 mg/m², and will be repeated every 4 weeks. This will be repeated for up to 12 cycles.
Experimental: Temozolomide + Bevacizumab Biological: Bevacizumab
Bevacizumab (vial of 400mg/16mL) at a dose of 10 mg/kg bodyweight i.v. in 90 min on day 1 and day 14 of 4 week cycles
Drug: Temozolomide
Temozolomide (250, 100, 20 and 5 mg caps) will be administered orally on day 1-5, 150-200 mg/m², and will be repeated every 4 weeks. This will be repeated for up to 12 cycles.

Detailed Description:

OBJECTIVES:

Primary

  • To document the activity of both combination temozolomide plus bevacizumab and temozolomide alone in patients with recurrent grade II or grade III glioma without 1p/19q co-deletion.

Secondary

  • To characterize the safety of treatment in these patients.
  • To document the quality of life and cognitive functioning, as a measure of clinical benefit, of these patients.
  • To explore qualification or occurrence of prognostic and/or predictive biomarkers of activity or efficacy in these patients. (exploratory)
  • To document the discordances between RANO and Macdonald's criteria for the evaluation of response and progression. (exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to institution, initial histology (grade II vs grade III), WHO performance status (0-1 vs 2), and prior treatment (radiotherapy [RT] alone, temozolomide [TMZ] or procarbazine, lomustine and vincristine [PCV] alone vs TMZ/RT). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral temozolomide as in arm I and bevacizumab IV over 90 minutes on days 1 and 15. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Patients complete neurocognitive questionnaires (i.e., the Hopkins Verbal Learning test, the Controlled Oral Word Association test, and the Trail Making tests A and B). Quality-of-life assessment questionnaires, including EORTC QLQ-C30 and EORTC-BN20, are completed by both patients and caregivers/relatives at baseline and then periodically.

Frozen tumor biopsies or paraffin blocks and blood specimens are collected for bio-banking and translational research.

After completion of study therapy, patients are followed up every 3 months.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of the following:

    • Grade II or grade III astrocytoma, oligodendroglioma, or oligoastrocytoma according to the WHO 2007
    • Absence of 1p/19q co-deletion
  • Tumor recurrence by MRI scan following initial therapy with radiotherapy or chemotherapy

    • Recurrent disease of non-operated patients must be ≥ 1 bidimensionally measurable contrast-enhancing lesion with clearly defined margins by MRI scan (minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart) done within the past two weeks
    • Must have stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan
  • Tissue samples available

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • ANC ≥ 1.5 x 10^9 cells/L
  • Platelet count ≥ 100 x 10^9 cells/L
  • Hemoglobin ≥ 9.9 g/dL
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2.5 times ULN
  • AST and ALT < 2.5 times ULN
  • INR < 1.5 times ULN
  • aPTT ≤ 1.5 times ULN
  • Calculated or measured creatinine clearance > 30 mL/min
  • Urine protein < 2+ by urine dipstick OR 24-hour urine protein < 1,000 mg
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective (non-hormonal) contraception during study and for ≥ 6 months after completion of study treatment
  • No other malignancies, except for that which was treated with curative intent more than 5 years prior to randomization or adequately controlled limited basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • No significant traumatic injury in the past 4 weeks
  • No cardiovascular disorder including, but not limited to, any of the following:

    • History of myocardial infarction or unstable angina within the past 6 months
    • NYHA class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months
    • History of hypertensive crisis or hypertensive encephalopathy
    • Inadequately controlled hypertension (defined as systolic blood pressure [BP] > 150 mm Hg and/or diastolic BP > 100 mm Hg)
  • No history of thrombotic or hemorrhagic event including, but not limited to, any of the following:

    • Recent hemorrhage on MRI of the brain (patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, and presence of punctate hemorrhage in the tumor are allowed)
    • Inherited bleeding diathesis or coagulopathy with the risk of bleeding
    • Arterial or venous thrombosis within the past 12 months
    • Stroke or transient ischemic attack within the past 6 months
    • Pulmonary hemorrhage/hemoptysis ≥ grade 2 (NCI-CTCAE version 4.0) within the past 4 weeks
  • No known hypersensitivity to any of the following:

    • Bevacizumab or temozolomide formulations
    • Chinese hamster ovary cell products or other recombinant human or humanized antibody
  • No underlying or prior conditions that could interfere with treatment including, but not limited to, any of the following:

    • History of intracranial abscess within the past 6 months
    • Clinically serious (as judged by the investigator) non-healing wounds, active skin ulcers, or incompletely healed bone fracture
    • History of active gastroduodenal ulcer(s)
    • History of abdominal fistula, non-gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
    • Active infection requiring hospitalization or antibiotics within the past 2 weeks
    • Other diseases interfering with follow up
  • No psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior treatment with bevacizumab or other VEGF inhibitors or VEGF-receptor signaling inhibitors
  • No more than 1 line of chemotherapy (concurrent and adjuvant temozolomide, or procarbazine, lomustine, or vincristine chemotherapy is considered 1 line of chemotherapy) for more than 6 months without progression
  • At least 4 weeks since prior and no other concurrent investigational drugs or anticancer agents
  • At least 3 months since radiotherapy prior to the diagnosis of progression

    • No radiotherapy with a dose over 65 Gy, stereotactic radiosurgery, or brachytherapy unless the recurrence is histologically proven
  • No invasive procedures (e.g., surgical resection, open biopsy, or any other major surgery involving entry into a body cavity) within the past 4 weeks

    • May have undergone surgery for recurrence (residual and measurable disease after surgery is not required but histology must have confirmed the recurrence)
    • Craniotomy or intracranial biopsy site must be adequately healed, free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization
  • No anticipation of the need for major surgery during the course of the study treatment
  • No core biopsy (excluding intracranial biopsy) or other minor surgical procedure within the past 7 days

    • Placement of a central vascular access device performed ≥ 2 days prior to bevacizumab administration is allowed
  • At least 10 days since prior aspirin (> 325 mg/day) or other NSAID with anti-platelet activity, or treatment with dipyramidole, ticlopidine, clopidogrel, or cilostaz
  • No full-dose anticoagulants at baseline, but prevention of thrombosis with low-dose anticoagulant allowed
  • No concurrent prophylactic use of growth factors, but red cell transfusions or erythropoietin allowed
  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: NCT01164189

Contacts
Contact: Davide Musmeci, PhD davide.musmeci@eortc.be

Locations
Austria
Landesnervenklinik Wagner Jauregg Recruiting
Linz, Austria
Medical University Vienna - General Hospital AKH Recruiting
Vienna, Austria
Belgium
Universitair Ziekenhuis Brussel Recruiting
Brussel, Belgium
U.Z. Leuven - Campus Gasthuisberg Recruiting
Leuven, Belgium
France
CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer Recruiting
Lyon, France
Assistance Publique - Hôpitaux de Marseille - Hôpital de La Timone Recruiting
Marseille, France
CHU de Nice - Hopital Pasteur Recruiting
Nice, France
CHU Pitie-Salpetriere Recruiting
Paris, France
Institut Gustave Roussy Recruiting
Paris, France
Centre Eugene Marquis Recruiting
Rennes, France
Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau Recruiting
Saint - Herblain, France
Centre Paul Strauss Recruiting
Strasbourg, France
Germany
Universitaetsklinikum Bonn Recruiting
Bonn, Germany
Klinikum Der J.W. Goethe Universitaet Recruiting
Frankfurt am Main, Germany
Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital Recruiting
Heidelberg, Germany
Universitaetskliniken Regensburg Recruiting
Regensburg, Germany
Israel
Rambam Medical Center Recruiting
Haifa, Israel
Italy
Ospedale Bellaria Recruiting
Bologna, Italy
Netherlands
Medisch Centrum Haaglanden - Westeinde Recruiting
Den Haag, Netherlands
Academisch Ziekenhuis Maastricht Recruiting
Maastricht, Netherlands
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands
Daniel Den Hoed Cancer Center at Erasmus Medical Center Recruiting
Rotterdam, Netherlands
Switzerland
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland
UniversitaetsSpital Zurich - Division of Oncology Recruiting
Zurich, Switzerland
United Kingdom
NHS Lothian - Western General Hospital Recruiting
Edinburgh, United Kingdom
Leeds Teaching Hospitals NHS Trust - St. James's University Hospital Recruiting
Leeds, United Kingdom
University College Hospital Recruiting
London, United Kingdom
Freeman Hospital, Northern Centre For Cancer Care Recruiting
Newcastle upon Tyne, United Kingdom
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Hoffmann-La Roche
Investigators
Study Chair: Martin J. van Den Bent, MD Daniel Den Hoed Cancer Center at Erasmus Medical Center
Study Chair: Ahmed Idbaih CHU Pitie-Salpetriere
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01164189     History of Changes
Other Study ID Numbers: EORTC-26091, 2009-017422-39
Study First Received: July 15, 2010
Last Updated: November 4, 2013
Health Authority: Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Israel: Ethics Commission
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adult anaplastic astrocytoma
adult diffuse astrocytoma
adult pilocytic astrocytoma
adult pineal gland astrocytoma
adult subependymal giant cell astrocytoma
adult oligodendroglioma
adult anaplastic oligodendroglioma
recurrent adult brain tumor
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
adult mixed glioma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Bevacizumab
Temozolomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 02, 2014