Clinical trial NCT01474239: A Study of Avastin (Bevacizumab) And Fotemustine in Patients With Recurrent Glioblastoma
Official title: Randomized Non Comparative Phase II Trial With Bevacizumab and Fotemustine in the Treatment of Recurrent Glioblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-11-18
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, non-comparative study will evaluate the efficacy and safety of Avastin (bevacizumab) in patients with recurrent glioblastoma. Patients will be randomized to receive Avastin 10 mg/kg intravenously every 2 weeks or fotemustine 75 mg/m2 on days 1, 8 and 15, followed by, after a 5 weeks interval, 100 mg/m2 intravenously every 3 weeks. Treatment with fotemustine serves as a calibration arm and no formal efficacy comparison will be made between the two treatment arms. The anticipated time of study treatment is until disease progression or unacceptable toxicity.


Eligibility criteria: Inclusion Criteria:

* Adult patients, \>/=18 years of age
* Diagnosis of recurrent glioblastoma multiforme (Grade IV)
* Previous treatment with temozolomide and radiotherapy
* First recurrence after standard adjuvant treatment (surgery, followed by radiotherapy and chemotherapy)
* Adequate hematological, biochemical and organ functions

Exclusion Criteria:

* Previous treatment with Avastin or other anti-angiogenic drugs
* Residual relevant toxicity resulting from previous therapy
* Radiotherapy within the 3 months prior to the diagnosis of disease progression
* Chemotherapy in the previous 4 weeks
* Other active or inactive malignancies (except for carcinoma in situ of the cervix, of the prostate or basal cell carcinoma)
* Clinically significant cardiovascular diseases

Primary outcomes:
measure: Percentage of Participants Alive 6 Months After Start of Treatment
timeFrame: 6 months
measure: Overall Survival (OS)
timeFrame: Baseline until death (up to 691 days)
Secondary outcomes:
measure: Percentage of Participants Who Were Alive and Progression Free 6 Months After Start of Treatment
timeFrame: 6 months
measure: Progression-Free Survival (PFS)
timeFrame: Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)
measure: Percentage of Participants Alive 9 Months After Start of Treatment
timeFrame: 9 months
measure: Percentage of Participants Alive 12 Months After Start of Treatment
timeFrame: 12 months
measure: Percentage of Participants Alive 30 Days After Last Dose of Study Drug
timeFrame: 30 days after last dose of study drug (up to Day 600)
measure: Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days)
measure: Change From Screening in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores at Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72
timeFrame: Screening, Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72
measure: Percentage of Participants With Corticosteroid Initiation During the Study Period
timeFrame: Baseline until recurrence (up to 691 days)
measure: Time to Corticosteroid Initiation
timeFrame: Baseline until recurrence (up to 691 days)
measure: Percentage of Participants in Each Class of Corticosteroid Use
timeFrame: Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, post-treatment follow-up (up to Day 691)
measure: Percentage of Participants With Karnofsky Performance Status (KPS) Deterioration
timeFrame: Baseline until KPS deterioration (up to 691 days)
measure: Time to Karnofsky Performance Status (KPS) Deterioration
timeFrame: Baseline until KPS deterioration (up to 691 days)
measure: Percentage of Participants With World Health Organization (WHO) Performance Status (PS) Deterioration
timeFrame: Baseline until WHO PS deterioration (Up to 691 days)
measure: Time to WHO PS Deterioration
timeFrame: Baseline until WHO PS deterioration (Up to 691 days)
Other outcomes:
Locations:
city: Napoli
country: Italy
state: Campania
city: Bologna
country: Italy
state: Emilia-Romagna
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: San Giovanni Rotondo
country: Italy
state: Puglia
city: Terni
country: Italy
state: Umbria
city: Padova
country: Italy
state: Veneto
city: Treviso
country: Italy
state: Veneto
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Brandes AA, Finocchiaro G, Zagonel V, Reni M, Caserta C, Fabi A, Clavarezza M, Maiello E, Eoli M, Lombardi G, Monteforte M, Proietti E, Agati R, Eusebi V, Franceschi E. AVAREG: a phase II, randomized, noncomparative study of fotemustine or bevacizumab for patients with recurrent glioblastoma. Neuro Oncol. 2016 Sep;18(9):1304-12. doi: 10.1093/neuonc/now035. Epub 2016 Mar 6.