A Study of Temsirolimus and Bevacizumab in Recurrent Glioblastoma Multiforme

This study has been completed.

Sponsor:

Collaborators:

University of Copenhagen

Wyeth is now a wholly owned subsidiary of Pfizer

Roche, Copenhagen

Information provided by:

Rigshospitalet, Denmark

ClinicalTrials.gov Identifier:

NCT00800917

First received: December 1, 2008

Last updated: June 1, 2010

Last verified: April 2010

History of Changes

Tracking Information
First Received Date ^ICMJE	December 1, 2008
Last Updated Date	June 1, 2010
Start Date ^ICMJE	November 2008
Primary Completion Date	February 2010 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: December 10, 2008)	Progression-free survival in months [ Time Frame: From start of treatment to death or progression ] [ Designated as safety issue: No ]
Original Primary Outcome Measures ^ICMJE (submitted: December 1, 2008)	Progression-free survival [ Designated as safety issue: No ]
Change History	Complete list of historical versions of study NCT00800917 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: October 1, 2009)	Adverse events [ Time Frame: every 2 weeks ] [ Designated as safety issue: Yes ] Objective tumor response rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: Yes ] Pre- vs post-treatment measurements of biomarkers and vascular system/immune system parameters [ Time Frame: weekly for the first 4 weeks, then every 8 weeks ] [ Designated as safety issue: Yes ] Correlation with biomarkers [ Time Frame: at the end of the study ] [ Designated as safety issue: Yes ]
Original Secondary Outcome Measures ^ICMJE (submitted: December 1, 2008)	Adverse events [ Designated as safety issue: Yes ] Objective tumor response rate [ Designated as safety issue: Yes ] Pre- vs post-treatment measurements of biomarkers and vascular system/immune system parameters [ Designated as safety issue: Yes ] Correlation with biomarkers [ Designated as safety issue: Yes ]
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	A Study of Temsirolimus and Bevacizumab in Recurrent Glioblastoma Multiforme
Official Title ^ICMJE	A Phase II Study of Temsirolimus and Bevacizumab in Recurrent Glioblastoma Multiforme
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
Detailed Description	Not Provided
Study Type ^ICMJE	Interventional
Study Phase	Phase 2
Study Design ^ICMJE	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Condition ^ICMJE	Glioblastoma Multiforme
Intervention ^ICMJE	Drug: Temsirolimus 25 mg weekly IV Drug: Bevacizumab 10 mg/kg every 2 weeks
Study Arm (s)	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Completed
Enrollment ^ICMJE	12
Completion Date	February 2010
Primary Completion Date	February 2010 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	Inclusion Criteria: 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 Platelet count ≥ 100,000/mm³ Bilirubin and phosphate normal AST and ALT ≤ 2.5 times upper limit of normal Creatinine normal OR creatinine clearance ≥ 60 mL/min Urine protein: creatinine ratio < 1.0 OR 24-hour urine protein < 1,000 mg Fasting cholesterol < 350 mg/dL (cholesterol medications are allowed) Fasting triglycerides < 400 mg/dL PT INR ≤ 1.5 Hematocrit < 41% (for males) or < 38% (for females) Fertile females must use an approved contraceptive (p-pills, IUD, depot injection of gestagen, subdermal implantation, hormonal vaginal ring or transdermal depot plaster), throughout the study and 3 months after discontinuation of study drugs. Fertile men must use dobbelt barrier method (preservative with sperm inhibiting creme) or female partner uses the above mentioned contraceptive. Fertile males must use preservatives. Exclusion Criteria: 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 Abdominal fistula Gastrointestinal perforation Intra-abdominal abscess Serious or nonhealing wound, ulcer, or bone fracture Psychiatric illness or social situations that would preclude study compliance Uncontrolled diabetes Hemoglobin A1c > 7% Concurrent non-study related surgical procedures Concurrent treatment with CYP3A4 inducers or inhibitors Other concurrent anticancer agents or therapies Significant traumatic injury within the past 28 days History of allergic reactions to compounds of similar chemical or biological composition to temsirolimus or bevacizumab Hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (e.g., infliximab) Pregnancy or nursing Patients previously intolerant to bevacizumab Anticoagulant therapy
Gender	Both
Ages	18 Years and older
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	Denmark

Administrative Information
NCT Number ^ICMJE	NCT00800917
Other Study ID Numbers ^ICMJE	BEV-CCI-779-GBM-02, Eudract no.: 2008-003679-40
Has Data Monitoring Committee	No
Responsible Party	Ulrik Lassen, MD, PH.D., Rigshospitalet
Study Sponsor ^ICMJE	Rigshospitalet, Denmark
Collaborators ^ICMJE	University of Copenhagen Wyeth is now a wholly owned subsidiary of Pfizer Roche, Copenhagen
Investigators ^ICMJE	Not Provided
Information Provided By	Rigshospitalet, Denmark
Verification Date	April 2010
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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