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

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:

MedlinePlus related topics: Cancer

Drug Information available for: Bevacizumab

U.S. FDA Resources

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.

Estimated Enrollment:	22
Study Start Date:	June 2010
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	June 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.

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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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01332929

Contacts

Contact: LEVY Christelle, MD

(+33) 2 31 45 50 02

c.levy@baclesse.fr

Locations

France
Centre François Baclesse	Recruiting
Caen, France, 14076
Contact: LEVY Christelle, MD (+33) 2 31 45 50 02 c.levy@baclesse.fr
Sub-Investigator: JOLY-LOBBEDEZ Florence, Pr
Principal Investigator: LEVY Christelle, MD
Sub-Investigator: GUNZER Katharina, MD
Sub-Investigator: GERVAIS Radj, MD
Sub-Investigator: SEVIN Emmanuel, MD
Sub-Investigator: SEGURA Carine, MD
Sub-Investigator: ALLOUACHE Djelila, MD
Sub-Investigator: HRAB Ioana, MD
Centre Oscar Lambret	Active, not recruiting
Lille, France, 59020
Centre Léon Bérard	Active, not recruiting
Lyon, France, 69373
Institut Curie	Recruiting
Paris, France, 75248
Contact: KIROVA Youlia, MD (+33) 1 44 32 40 50 youlia.kirova@curie.net
Principal Investigator: KIROVA Youlia, MD
Sub-Investigator: FOURQUET Alain, MD
Sub-Investigator: BOLLET Marc, MD
Sub-Investigator: CAMPANA François, MD
Sub-Investigator: DENDALE Remi, MD
Sub-Investigator: DIERAS Véronique, MD
Sub-Investigator: PIERGA Jean-Yves, MD
Sub-Investigator: COTTU Paul-Henri, MD
Sub-Investigator: LE TOURNEAU Christophe, MD
Sub-Investigator: TRESCA Patricia, MD
Centre Henri Becquerel	Recruiting
Rouen, France, 76038
Contact: LEHEURTEUR Marienne, MD (+33) 2 32 08 29 28 mleheurteur@rouen.fnclcc.fr
Principal Investigator: LEHEURTEUR Marianne, MD
Sub-Investigator: HANZEN Chantal, MD
Sub-Investigator: MOLDOVAN Christian, MD
Centre René Gauducheau	Recruiting
St Herblain, France, 44805
Contact: SUPIOT Stephane, MD (+33) 2 40 67 99 03 s-supiot@nantes.fnclcc.fr
Principal Investigator: SUPIOT Stephane, MD
Sub-Investigator: MAHE Marc-André, MD
Sub-Investigator: LEBLANC-ONFROY Magali, MD
Sub-Investigator: AUMONT LE GUILCHER Maud, MD
Sub-Investigator: THILLAYS François, MD
Sub-Investigator: CAMPONE Mario, MD

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:	February 7, 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:

Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Neoplasms, Second Primary
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 May 21, 2013