Safety Evaluation of a Combination of Brain Radiation Therapy and Bevacizumab (Avastin®) for Treatment of Brain Metastasis

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute, France
Roche Pharma AG
Institut Curie
Information provided by (Responsible Party):
Centre Francois Baclesse
ClinicalTrials.gov Identifier:
NCT01332929
First received: April 5, 2011
Last updated: September 11, 2013
Last verified: September 2013
  Purpose

This phase I pilot study aims to define the safety of a combined treatment of bevacizumab and whole brain radiation therapy for the treatment of patients with brain metastasis of solid tumors. If this therapeutic scheme confirms it's safety profile, the investigators can expect:

  • first, to allow that all patients can receive bevacizumab for their advanced and/or metastatic cancer if necessary, even in case of brain metastasis.
  • Secondly, if this trial confirm a synergic effect of the combination of angiogenesis inhibitors and brain radiotherapy for local control of brain metastasis, an improvement of the therapeutic results for these patients which have a poor hope of survival and for which none innovative approach is currently suggested.

Moreover, the investigators hope that the analysis of the different data of MRI evaluation - morphological and functional - will allow better definition of radiological evaluation of the therapeutic effect of angiogenesis inhibitors on brain metastasis.


Condition Intervention Phase
Metastatic Malignant Neoplasm to Brain
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety Evaluation of a Combination of Brain Radiation Therapy and Bevacizumab (Avastin®) for Treatment of Brain Metastasis

Resource links provided by NLM:


Further study details as provided by Centre Francois Baclesse:

Primary Outcome Measures:
  • The Maximal Tolerated dose (MTD) [ Time Frame: The MTD will be evaluated 6 weeks after the first administration ob bevacizumab ] [ Designated as safety issue: Yes ]
    The primary objective is to determine the Maximal Tolerated Dose (MTD) of the combination of bevacizumab and whole brain radiation therapy for patients with brain metastases


Secondary Outcome Measures:
  • Tumor regression [ Time Frame: The first evaluation will be performed 2 weeks after the first injection, 6 weeks after the end of radiotherapy and each 3 months ] [ Designated as safety issue: No ]
    The secondary objective is to assess the treatment-related parameters of tumor regression by a morphologic and functional MRI six weeks after the end of the treatment.


Enrollment: 21
Study Start Date: June 2010
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab
first level dose : 5 mg/kg Second level dose : 10 mg/kg Third level dose : 15 mg/kg
Drug: Bevacizumab

5, 10 or 15 mg/kg, IV, on day 1, 15 and 29 plus radiation therapy of the whole brain.

For level 0,1 and 2, a total dose of 30 Gy will be administered in 15 fractions of 2 Gy, from D15 to D33 with 5 fractions a week.

For level 3,a total dose of 30 Gy will be administered in 10 fractions of 3 Gy, from D15 to D26 with 5 fractions a week.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 < age < 70 man or woman
  • Patient with a cytologically or histologically proven primary solid tumor
  • With measurable and inoperable brain metastasis,
  • Without meningeal carcinomatosis ,
  • ECOG performance status ≤ 2,
  • No previous treatment with angiogenesis inhibitors less than 3 months before inclusion,
  • No chemotherapy and/or immunotherapy less than 3 weeks before treatment,
  • No contra-indication to bevacizumab,
  • No proteinuria with urine dipstick for proteinuria > 2+
  • Blood sample ≤ 7 days before inclusion:
  • Hemoglobin ≥ 10 G/100 ml
  • Neutrophils count ≥ 1500 /mm3
  • Platelets ≥ 100 000 /mm3
  • Normal coagulation test: INR ≤ 1,5 ET TCA ≤ 1,5 x LSN 7 days before inclusion
  • A written informed consent must be obtained.

Exclusion Criteria:

  • Haemorrhagic brain metastasis,
  • Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg). Patients with high initial blood pressure are eligible if entry criteria are met after initiation or adjustment of antihypertensive medication,
  • Prior brain radiation therapy
  • Concomitant anticoagulant treatment
  • Significant surgical procedure less than 28 days before inclusion (1 day if minor surgical act)
  • Significant cardio-vascular disease, eg:
  • Cerebral vascular thrombosis/haemorrhage or myocardial infarction <6 months
  • Congestive heart failure > 2 NYHA
  • Uncontrolled coronary disease
  • Prior venous and/or arterial thrombosis < 6 months before inclusion
  • Severe concurrent uncontrolled medical disease,
  • Any psychiatric disorder that might prevent the subject from completing the treatment or interfere with the interpretation of the study results,
  • Pregnancy or breast feeding
  • Individual deprived of liberty or placed under the authority of a tutor.
  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: NCT01332929

Locations
France
Centre François Baclesse
Caen, France, 14076
Centre Oscar Lambret
Lille, France, 59020
Centre Léon Bérard
Lyon, France, 69373
Institut Curie
Paris, France, 75248
Centre Henri Becquerel
Rouen, France, 76038
Centre René Gauducheau
St Herblain, France, 44805
Sponsors and Collaborators
Centre Francois Baclesse
National Cancer Institute, France
Roche Pharma AG
Institut Curie
Investigators
Principal Investigator: Christelle LEVY, MD Centre François Baclesse
  More Information

No publications provided

Responsible Party: Centre Francois Baclesse
ClinicalTrials.gov Identifier: NCT01332929     History of Changes
Other Study ID Numbers: REBECA
Study First Received: April 5, 2011
Last Updated: September 11, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Francois Baclesse:
brain radiation therapy
Bevacizumab
brain metastasis
solid tumor

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Brain Neoplasms
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014