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

NCT01332929 | Completed Phase 1 DMC

• 1 other identifier: REBECA
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Metastatic Malignant Neoplasm to Brain

Keywords

brain radiation therapy; Bevacizumab; brain metastasis; solid tumor

Outcome Measures

Primary Outcomes (1)

• The Maximal Tolerated dose (MTD)

  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

  The MTD will be evaluated 6 weeks after the first administration ob bevacizumab

Secondary Outcomes (1)

• Tumor regression

  The first evaluation will be performed 2 weeks after the first injection, 6 weeks after the end of radiotherapy and each 3 months

Study Arms (1)

Bevacizumab

EXPERIMENTAL

first level dose : 5 mg/kg Second level dose : 10 mg/kg Third level dose : 15 mg/kg

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

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.

Bevacizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \< 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 chemotherapy and/or immunotherapy less than 3 weeks before treatment,
• No contra-indication to bevacizumab,
• No proteinuria with urine dipstick for proteinuria \> 2+
• Hemoglobin ≥ 10 G/100 ml
• Neutrophils count ≥ 1500 /mm3
• Platelets ≥ 100 000 /mm3
• A written informed consent must be obtained.

You may not qualify if:

• 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 cardio-vascular disease, eg:
• Cerebral vascular thrombosis/haemorrhage or myocardial infarction \<6 months
• Congestive heart failure \> 2 NYHA
• Uncontrolled coronary disease
• 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.

Sponsors & Collaborators

• Centre Francois Baclesse: lead
• National Cancer Institute, France: collaborator
• Roche Pharma AG: collaborator
• Institut Curie: collaborator

Study Sites (6)

Centre François Baclesse

Caen, 14076, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Curie

Paris, 75248, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Centre René Gauducheau

Saint-Herblain, 44805, France

Location

Related Publications (1)

• Levy C, Allouache D, Lacroix J, Dugue AE, Supiot S, Campone M, Mahe M, Kichou S, Leheurteur M, Hanzen C, Dieras V, Kirova Y, Campana F, Le Rhun E, Gras L, Bachelot T, Sunyach MP, Hrab I, Geffrelot J, Gunzer K, Constans JM, Grellard JM, Clarisse B, Paoletti X. REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours. Ann Oncol. 2014 Dec;25(12):2351-2356. doi: 10.1093/annonc/mdu465. Epub 2014 Oct 1.

  PMID: 25274615 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christelle LEVY, MD

  Centre François Baclesse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2011
• First Posted: April 11, 2011
• Study Start: June 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: September 12, 2013

Record last verified: 2013-09

Locations

FR (6)