Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01474239
Other study ID # ML25739
Secondary ID
Status Completed
Phase Phase 2
First received November 8, 2011
Last updated February 16, 2016
Start date November 2011
Est. completion date December 2013

Study information

Verified date September 2015
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority Italy: Ministry of Health
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 91
Est. completion date December 2013
Est. primary completion date December 2013
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
bevacizumab [Avastin]
10 mg/kg every 2 weeks intravenously until disease progression or unacceptable toxicity
fotemustine
75 mg/m2 intravenously on days 1, 8 and 15 followed by, after a 5 weeks interval, 100 mg/m2 on day 1 of a 3-weeks cycle. Until disease progression or unacceptable toxicity

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants Alive 6 Months After Start of Treatment Overall survival (OS) was defined as the time in months from the start of treatment to death due to any cause. If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of magnetic resonance imaging (MRI) assessment, date of last treatment, date of discontinuation and date of last available follow-up visit. Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method. 6 months No
Primary Overall Survival (OS) OS was defined as the time in months from the start of treatment to death due to any cause. If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit. Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method. Baseline until death (up to 691 days) No
Secondary Percentage of Participants Who Were Alive and Progression Free 6 Months After Start of Treatment Progression-free survival (PFS) was defined as the time in months from the start of treatment to the date of the first occurrence of disease progression or death from any cause, whichever occurred first. PFS was estimated by the Kaplan-Meier method. Progression was assessed using Response Assessment in Neuro-Oncology (RANO) or Macdonald Response Criteria, whichever occurred first. As per the RANO criteria, progression was defined as 25% or more increase in enhancing lesions despite stable or increasing steroid dose; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease). As per the Macdonald criteria, progression was defined as 25% or more increase in enhancing lesions; any new lesions; and clinical deterioration. 6 months No
Secondary Progression-Free Survival (PFS) PFS was defined as the time in months from the start of treatment to the date of the first occurrence of disease progression or death from any cause, whichever occurred first. PFS was estimated by the Kaplan-Meier method. Progression was assessed using the RANO or the Macdonald Response Criteria, whichever occurred first. As per RANO criteria, progression was defined as 25% or more increase in enhancing lesions despite stable or increasing steroid dose; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease). As per Macdonald criteria, progression was defined as 25% or more increase in enhancing lesions; any new lesions; and clinical deterioration. Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days) No
Secondary Percentage of Participants Alive 9 Months After Start of Treatment OS was defined as the time in months from the start of treatment to death due to any cause. If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit. Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method. 9 months No
Secondary Percentage of Participants Alive 12 Months After Start of Treatment OS was defined as the time in months from the start of treatment to death due to any cause. If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit. Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method. 12 months No
Secondary Percentage of Participants Alive 30 Days After Last Dose of Study Drug OS was defined as the time in months from the start of treatment to death due to any cause. If a participant was not known to have died, time was censored at the last date the participant was known to be alive, which was defined as the latest among date of last visit, date of last sample collected for laboratory exam, date of MRI assessment, date of last treatment, date of discontinuation and date of last available follow-up visit. Participants with no information after baseline were censored at Day 1. OS was estimated by the Kaplan-Meier method. 30 days after last dose of study drug (up to Day 600) No
Secondary Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) Percentage of participants achieving CR or PR as overall response between first drug administration and documented disease progression were calculated. Tumor response was evaluated according to both the RANO and the Macdonald response criteria. As per Macdonald criteria, CR was defined as the disappearance of all enhancing disease, sustained for at least 4 weeks, and no new lesions along with clinical features of clinically stable or improved, with no corticosteroid; PR was defined as a 50% or more decrease of all measurable enhancing lesions, sustained for at least 4 weeks, and no new lesion along with clinical features of clinically stable or improved, with stable or reduced corticosteroids. RANO criteria defined CR and PR the same as Macdonald criteria with the following additions: CR - improved non enhancing T2/FLAIR lesions; PR - no progression of non-measurable disease, stable or improved non enhancing FLAIR/T2 lesions. Baseline until disease progression or death (baseline, 46 days after first administration of study drug, and thereafter every 56 days up to 691 days) No
Secondary 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 EORTC QLQ-C30: included global health status/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global QOL/functional scales indicates better level of QOL/functioning, or a higher score for symptom scale indicates greater degree of symptoms. Screening, Weeks 8, 16, 24, 32, 40, 48, 56, 64, and 72 No
Secondary Percentage of Participants With Corticosteroid Initiation During the Study Period Corticosteroid initiation was assessed in participants not receiving corticosteroids at screening. The participant had the event if he/she started on corticosteroids with a dosage greater than equal to (>/=) 2 mg dexamethasone equivalent. Baseline until recurrence (up to 691 days) No
Secondary Time to Corticosteroid Initiation Time to corticosteroid initiation was defined as the time from screening to the start date of the first corticosteroid administration in participants not receiving corticosteroids at screening. The participant had the event if he/she started on corticosteroids with a dosage =2 mg dexamethasone equivalent. Instead, if the participant was not known to have the event, time was censored at the last available visit date. Time to corticosteroid initiation was estimated using Kaplan Meier method. Baseline until recurrence (up to 691 days) No
Secondary Percentage of Participants in Each Class of Corticosteroid Use Corticosteroid use was classified as: 1. No Change (if corticosteroid dose at each assessment was equal to baseline); 2. Decreased (if corticosteroid dose at each assessment was lower than baseline); 3. Increased (corticosteroid dose at each assessment was greater than baseline). Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, post-treatment follow-up (up to Day 691) No
Secondary Percentage of Participants With Karnofsky Performance Status (KPS) Deterioration Deterioration of KPS was defined as a decrease of at least 20 percentage points with respect to the screening. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks. Baseline until KPS deterioration (up to 691 days) No
Secondary Time to Karnofsky Performance Status (KPS) Deterioration Time to KPS deterioration was defined as the time from screening to the first date of deterioration of the KPS score. Deterioration of KPS was defined as a decrease of at least 20 percentage points with respect to the screening. KPS is an 11-level score which ranges between 0 (death) to 100 (complete healthy status); a higher score represents a higher ability to perform daily tasks. Time to KPS deterioration was estimated using Kaplan Meier method. If the participant was not known to have the event, time was censored at the last available visit date. Baseline until KPS deterioration (up to 691 days) No
Secondary Percentage of Participants With World Health Organization (WHO) Performance Status (PS) Deterioration WHO PS deterioration was defined as a decrease of at least 1 point with respect to the screening value. WHO PS is a 6-level score which ranges between 0 (fully active) to 5 (death); a lower score represents a higher ability to perform daily tasks. Baseline until WHO PS deterioration (Up to 691 days) No
Secondary Time to WHO PS Deterioration Time to WHO PS deterioration was defined as the time from randomization to the first date of deterioration of the WHO performance status score. WHO PS deterioration was defined as a decrease of at least 1 point with respect to the screening value. WHO PS is a 6-level score which ranges between 0 (fully active) to 5 (death); a lower score represents a higher ability to perform daily tasks. Baseline until WHO PS deterioration (Up to 691 days) No
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05023551 - Study of DSP-0390 in Patients With Recurrent High-Grade Glioma Early Phase 1
Recruiting NCT06059690 - Biologic Association Between Metabolic Magnetic Resonance-positron Emission Tomograph (MR-PET) and Tissue Measures of Glycolysis in Brain Tumors of Infiltrating Glioblastoma Cells Phase 1/Phase 2
Recruiting NCT04116411 - A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients Phase 2
Terminated NCT01902771 - Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors Phase 1
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Completed NCT00038493 - Temozolomide and SCH66336 for Recurrent Glioblastoma Multiforme Phase 2
Withdrawn NCT03980249 - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells Early Phase 1
Recruiting NCT01923922 - CT Perfusion in the Prognostication of Cerebral High Grade Glioma N/A
Completed NCT01956734 - Virus DNX2401 and Temozolomide in Recurrent Glioblastoma Phase 1
Completed NCT01402063 - PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation Phase 2
Suspended NCT01386710 - Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma Phase 1/Phase 2
Completed NCT01301430 - Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme. Phase 1/Phase 2
Active, not recruiting NCT00995007 - A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas Phase 2
Terminated NCT01044966 - A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma Phase 1/Phase 2
Terminated NCT00990496 - A Study Using Allogenic-Cytomegalovirus (CMV) Specific Cells for Glioblastoma Multiforme (GBM) Phase 1
Completed NCT00402116 - Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients Phase 1/Phase 2
Completed NCT00112502 - Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme Phase 2
Completed NCT00504660 - 6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients Phase 2
Recruiting NCT05366179 - Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc Phase 1