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
  Purpose

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


Condition Intervention Phase
Glioblastoma Multiforme
Drug: Temsirolimus
Drug: Bevacizumab
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 Phase II Study of Temsirolimus and Bevacizumab in Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Progression-free survival in months [ Time Frame: From start of treatment to death or progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 12
Study Start Date: November 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Temsirolimus
    25 mg weekly IV
    Drug: Bevacizumab
    10 mg/kg every 2 weeks
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00800917

Locations
Denmark
Rigshospitalet
Copenhagen, Denmark
Sponsors and Collaborators
Rigshospitalet, Denmark
University of Copenhagen
Wyeth is now a wholly owned subsidiary of Pfizer
Roche, Copenhagen
  More Information

No publications provided

Responsible Party: Ulrik Lassen, MD, PH.D., Rigshospitalet
ClinicalTrials.gov Identifier: NCT00800917     History of Changes
Other Study ID Numbers: BEV-CCI-779-GBM-02, Eudract no.: 2008-003679-40
Study First Received: December 1, 2008
Last Updated: June 1, 2010
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

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
Sirolimus
Everolimus
Bevacizumab
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014