A Study of Bevacizumab and Extended Treatment of Temozolomide in Patients With Recurrent Glioblastoma Multiforme

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01115491
First received: April 30, 2010
Last updated: December 3, 2014
Last verified: December 2014
  Purpose
This is a Phase II, national, multicenter, open-label, non-comparative study to investigate the efficacy and safety of bevacizumab and temozolomide in patients with recurrent glioblastoma multiforme (GBM) after a first treatment failure. Patients will receive bevacizumab 10 mg/kg intravenously every two weeks until disease progression, consent withdrawal, or unacceptable toxicity. Anticipated time on study treatment is 12-24 months.

Condition Intervention Phase
Glioblastoma Multiforme
Drug: bevacizumab [Avastin]
Drug: temozolomide
Phase 2

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: A Single Arm Phase II Study of Bevacizumab and Extended Treatment of Temozolomide in Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) - Percentage of Participants With an Event [ Time Frame: Baseline (BL), every 28 days, until progression, death or end-of-study, an average of 32 weeks ] [ Designated as safety issue: No ]
    PFS was defined as the time, in weeks, from the date of inclusion in the study to the date of the first documentation of disease progression or death of the participant due to any cause. Participants that did not have an event at the time the analysis was performed were censored at the date of last contact. Participants that began a treatment other than those planned in this study (bevacizumab or temozolomide) were censored on the start date of the new treatment.

  • PFS - Time to Event [ Time Frame: BL, every 28 days, until progression, death or end-of-study, an average of 32 weeks ] [ Designated as safety issue: No ]
    PFS was defined as the time, in weeks, from the date of inclusion in the study to the date of the first documentation of disease progression or death of the participant due to any cause. Participants that did not have an event at the time the analysis was performed were censored at the date of last contact. Participants that began a treatment other than those planned in this study (bevacizumab or temozolomide) were censored on the start date of the new treatment. PFS was estimated using the Kaplan-Meier method.

  • PFS: Probability of Remaining Progression Free at 24 Weeks After Beginning the Study [ Time Frame: BL, 24 weeks (after 6th cycle) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival - Percentage of Participants With an Event [ Time Frame: BL, every 28 days, until death or end-of-study, an average of 32 weeks ] [ Designated as safety issue: No ]
    Overall survival was defined as the time transpired (in weeks) between the date of the participant's inclusion in the trial until the date of his/her death by any cause. Participants that were alive at the time the analysis was performed were censored on the date of last contact.

  • Overall Survival - Time to Event [ Time Frame: BL, every 28 days, until death or end-of-study, an average of 32 weeks ] [ Designated as safety issue: No ]
    Overall survival was defined as the time transpired (in weeks) between the date of the participant's inclusion in the trial until the date of his/her death by any cause. Participants that were alive at the time the analysis was performed were censored on the date of last contact. Median overall survival was estimated using the Kaplan-Meier method.

  • Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: BL, every 28 days, until progression, death or end-of-study, an average of 32 weeks ] [ Designated as safety issue: No ]
    Overall response was defined as the percentage of participants who obtained CR or PR using adapted MacDonald criteria. CR: disappearance of all index and non-index lesions, confirmed no less than 4 weeks after assessment, no evidence of disease progression; corticosteroid dosage at or below 20 mg hydrocortisone daily; no neurological changes or an improvement as compared to last disease assessment. PR was defined as: Fifty percent or greater decrease in the sum of products of the larger diameter and the larger perpendicular diameter of all index lesions confirmed no less than 4 weeks after assessment, no evidence of disease progression and the absence of progressive, or non-evaluable disease status for non-index legions; unchanged, or decreased corticosteroid dose as compared to the last disease assessment; no neurological changes or an improvement as compared to the neurological examination at last disease assessment.


Enrollment: 32
Study Start Date: June 2010
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: bevacizumab [Avastin]
Bevacizumab 10 mg/kg body weight will be administered intravenously every two weeks
Drug: temozolomide
Daily by the oral route (dose, 150 mg/m2) on days 1 to 7 and 15 to 21 of each cycle

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >= 18 years
  • Histological diagnosis of glioblastoma multiforme (GBM) documented by surgical resection or biopsy.
  • They should be patients in a first relapse treated with radiotherapy and chemotherapy and chemotherapy based on temozolomide 150-200 mg/m2 on days 1 to 5 every 28 days (Stupp regimen) for at least three cycles. At least 4 weeks must have lapsed since previous chemotherapy and 3 months since the last dose of radiotherapy.
  • Use of an effective contraceptive method by patients and their partners.
  • Stable or decreasing corticosteroid dose for the five days prior to study entry
  • Adequate hematological function
  • Adequate liver function
  • Adequate kidney function

Exclusion Criteria:

  • Signs of recent bleeding at the MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving bleeding changes related to surgery, and presence of punctate hemorrhage in the tumor will be allowed to participate in the study.
  • Prior treatment with bevacizumab
  • Poorly controlled arterial hypertension
  • History of hypertensive crises or hypertensive encephalopathy
  • New York Health Association (NYHA) Class II or higher congestive heart failure
  • History of myocardial infarction or unstable angina pectoris within six months of study entry
  • History of stroke or TIA within six months of study entry
  • Significant vascular disease within six months of study entry
  • History of hemoptysis > grade 2 according to the NCI CTC criteria within one month of study entry
  • Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgery, open biopsy, intracranial biopsy, ventriculoperitoneal shunt, or major traumatic lesion within 28 days of study entry.
  • Core needle biopsy (excluding intracranial biopsy) or other minor surgery within seven days of randomization. Placement of a central vascular access device (CVAD) if performed in the two days prior to bevacizumab administration
  • History of abdominal fistula or gastrointestinal perforation within six months of study entry
  • History of intracranial abscess within six months of randomization
  • Any prior malignant neoplasm treated with curative intent in the five years prior to study entry, except for adequately controlled limited basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix
  • Patients with any other metabolic or psychological disease
  • Hypersensitivity to products derived from Chinese hamster ovary cells or to other humanized or recombinant human antibodies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01115491

Locations
Spain
Barcelona, Spain, 08025
Barcelona, Spain, 08907
Barcelona, Spain, 08916
Madrid, Spain, 28040
Madrid, Spain, 28041
Madrid, Spain, 28046
Valencia, Spain, 41014
Valencia, Spain, 46026
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01115491     History of Changes
Other Study ID Numbers: ML25152  2010-019051-21 
Study First Received: April 30, 2010
Results First Received: May 28, 2014
Last Updated: December 3, 2014
Health Authority: Spain: Agencia Española del medicamento y productos sanitarios.

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Temozolomide
Dacarbazine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016