A Study of Temsirolimus and Bevacizumab in Recurrent Glioblastoma Multiforme

NCT00800917 | Completed Phase 2

• 2 other identifiers: BEV-CCI-779-GBM-02Eudract no.: 2008-003679-40
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is an investigator initiated, open label phase II study, where patient with recurrent primary GBM will be considered for the study. Only patients with recurrence after Temozolomide and VEGF-directed therapy with Bevacizumab will be considered for the study. Patients will receive temsirolimus 25 mg IV over 30-60 minutes on days 1, 8, 15 and 22 and bevacizumab 10 mg/kg IV over 30-90 minutes on day 8 and 22. Treatment repeats every 28 days for a maximum of 12 courses in the absence of disease progression or unacceptable toxicity. A safety analysis will be performed when the first 10 patients have received minimum 4 cycles (8 weeks). The study will then be stopped: If DLT is observed in \> 2/10 patients, Occurrence of any serious adverse events not described in the SPC of each agents, If partial remission is not observed in at least 1/10 patients

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (1)

• Progression-free survival in months

  From start of treatment to death or progression

Secondary Outcomes (4)

• Adverse events

  every 2 weeks

• Objective tumor response rate

  every 8 weeks

• Pre- vs post-treatment measurements of biomarkers and vascular system/immune system parameters

  weekly for the first 4 weeks, then every 8 weeks

• Correlation with biomarkers

  at the end of the study

Interventions

Temsirolimus DRUG

25 mg weekly IV

Bevacizumab DRUG

10 mg/kg every 2 weeks

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Histological verification of primary GBM and failure after radiotherapy and temozolomide (TMZ)
• Previously treated with VEGF-directed therapy with bevacizumab
• Previously received radiotherapy and temozolomide
• More than 4 weeks since any of the following prior treatments: chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• Radiotherapy to nontarget lesions or lesions that are not to be biopsied VEGF-directed therapy (including bevacizumab)
• Investigational agents
• More than 6 months since prior major surgery or open biopsy and recovered (only 6 weeks required if operation is for recurrent GBM)
• No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of the following:
• Temsirolimus
• Bevacizumab
• CYP450 isoenzymes
• ECOG performance status 0-1
• WBC ≥ 3,000 mm³
• Absolute neutrophil count ≥ 1,500/mm³

You may not qualify if:

• Clinically significant cardiovascular disease, including the following:
• Cerebrovascular accident within the past 6 months
• Transient ischemic attack within the past 6 months
• Myocardial ischemia within the past 6 months
• Myocardial infarction within the past 6 months
• Other thromboembolic event within the past 6 months
• Unstable angina within the past 6 months
• Uncontrolled hypertension (i.e., hypertension despite maximal therapy)
• New York Heart Association class II-IV heart disease
• Congestive heart failure
• Serious cardiac arrhythmia requiring medication
• Clinically significant peripheral vascular disease
• Uncontrolled intercurrent illness
• Ongoing or active infection
• One of the following within the past 6 months

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• University of Copenhagen: collaborator
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator
• Roche, Copenhagen: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, Denmark

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

temsirolimus; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 1, 2008
• First Posted: December 2, 2008
• Study Start: November 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: June 2, 2010

Record last verified: 2010-04

Locations

DK (1)