Phase III trial exploring the combination of bevacizumab and loumustine in patients with first recurrence of a glioblastoma.

Phase 1

• Conditions: Recurrent glioblastoma; MedDRA version: 18.1Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-023218-30-BE
• Lead Sponsor: EORTC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06-07
• Last Update Posted: 7 May 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 596

Inclusion Criteria

-Histologically confirmed de novo glioblastoma (primary) with
unequivocal first progression after RT (radiotherapy)
concurrent/adjuvant chemotherapy at least 3 months off the
concomitant part of the chemoradiotherapy.
-Availability of biological material for central review processes and
translational research projects.
-Patient may have been operated for recurrence. If operated:
*residual and measurable disease after surgery is not required but surgery must have confirmed the recurrence
*a post-surgery MRI should be available within 48 hours following surgery
*Surgery completed at least 2 weeks before registration and patients should have fully recovered
-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 randomisation.
-Absence of any cardiovascular disorder
-Absence of known hypersensitivity:
*to any part of the bevacizumab or lomustine formulations.
*to Chinese hamster ovary cell products or other recombinant human or humanized antibody.
-Age =18 years
-WHO Performance status 0-2
-Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study
subject. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Females should not be breast feeding.
-Males must agree to use an effective method of contraception durign the tratment period and for at least 6 months after the last study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 124
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion Criteria

-More than one line of chemotherapy (concurrent and adjuvant
temozolomide based chemotherapy including in combination with
another investigational agent is considered one line of chemotherapy). Chemotherapy must have been completed at least 4 weeks prior to randomization.
-Current or recent (within 4 weeks before randomization) treatment with another investigational drug.
-Prior treatment with bevacizumab or other VEGF inhibitors or VEGFReceptor signaling inhibitors.
-Radiotherapy within the three months prior to the diagnosis of
progression.
-Radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven.
-Prior treatment with nitrosoureas.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to investigate whether the addition of bevacizumab to lomustine improves overall survival (OS) in patients with recurrent glioblastoma copared to treatment with lomustine alone.;Secondary Objective: - Progression free survival distribution according to RANO criteria (PFS:distribution, PFS 6 and PFS12)<br>- Response distribution, objective response rate, duration of response (according to RANO criteria), progression pattern.<br>- Overall survival: distribution and OS 24<br>- Complete safety profile according to CTCAE version 4.0.<br>- Patient-oriented criteria: clinical/neurological deterioration free<br>survival, steroid use, quality of life (by patients and<br>caregivers/relatives) and development of cognitive deterioration.;Primary end point(s): Overall survival;Timepoint(s) of evaluation of this end point: Treatment effect measured by the hazard ration (HR)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progression Free Survival (PFS), Neurological Deterioration Free Survival (NDFS), best overall response distribution, objective and complete response, duration of objective or complete response.;Timepoint(s) of evaluation of this end point: Objective or comlete response rates, median OS, PFS, NDFS, objective or complete response duration. PFS6, PFS12, OS9, OS12, OS24, NDFS6, NDFS12.