Bevacizumab and Irinotecan for Patients With Primary Brain Tumors and Progression After Standard Therapy

This study has been completed.
Sponsor:
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00463203
First received: April 18, 2007
Last updated: June 27, 2011
Last verified: June 2011
  Purpose

Irinotecan has demonstrated activity in malignant gliomas in multiple phase II studies. The activity is limited, with an approximately 15 % response rate and a progression-free survival of 3-5 months. Given the synergy between irinotecan and bevacizumab in colorectal cancer, and the high-level expression of vascular endothelial growth factor on malignant gliomas, one would expect synergy between bevacizumab and irinotecan against gliomas.

Recent data form a small study of 32 patients from Duke University have achieved a response rate of 62% in patients with malignant gliomas. Most included patients had glioblastomas, but this regimen may also have activity in more rare primary malignant brain tumors. The investigators therefore plan to include other primary malignant brain tumors in this study, and the clinical activity will be correlated with biomarkers and PET results of metabolic activity and blood flow. This may result in information that can be used to individualize therapy in the future.


Condition Intervention Phase
Brain Neoplasms
Glioma
Drug: Bevacizumab
Drug: Irinotecan
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

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate - Response according to MacDonald criteria [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Adverse event according to CTCAE 3.0 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 54
Study Start Date: March 2007
Study Completion Date: June 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bevacizumab
    10 mg/kg every 2 weeks
    Drug: Irinotecan
    125 mg/m2 non-EIAED or 340 mg/m2 EIAED 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 malignant brain tumor, or grade II glioma, meningeoma or ependymoma with progression and no other treatment options (including brain stem gliomas without histological verification)
  • Recurrence or progression after standard treatment (debulking surgery of possible, radiotherapy and for grade III or IV tumors temozolomide or other chemotherapy.
  • Evidence of measurable recurrent progressive disease (CT/MRI scan)
  • An interval of at least 4 weeks between prior surgical resection and study enrollment
  • An interval of at least 4 weeks between prior radiotherapy or chemotherapy and enrollment on this protocol.
  • PS 0-2 (ECOG scale)
  • Age > 18
  • Life expectancy > 3 month
  • Normal organ function:
  • Platelets > 125 x 109/l
  • Hemoglobin >6,2 mmol/l
  • Leukocytes > 3 x 109/l
  • ACN> 1,5 x 109/l
  • ASAT or ALAT < 3 x upper normal limit
  • Bilirubin < 1,5 x upper normal limit
  • Creatinine clearance > 45 ml/min
  • APTT < normal limit
  • INR < normal limit
  • Fertile females must use oral contraceptive, IUD (intrauterine device), gestagen sustained release injection, subdermal implantation, transdermal patch or hormonal vaginal ring. This must continue at least three months after the patients is off-study. Fertile males must use preservatives
  • No sign of cerebral bleeding

Exclusion criteria:

  • Radiotherapy or chemotherapy within the last 4 weeks.
  • Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
  • Prior VEGF-based therapy
  • Any condition (medical, social, psychological), which would prevent adequate information and follow-up
  • Any other concurrent active malignancy, except, adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ.
  • Any significant cardiac disease (New York Heart Association Class II or greater), arrhythmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris.
  • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis, coagulopathy or taking ASA, NSAIDs or clopidogrel
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the curse of the study
  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to day 0
  • History of known HIV, Hepatitis B and Hepatitis C negative
  • Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound, ulcer or bone fracture
  • Pregnancy or breast feeding
  • Requires therapeutic anti-coagulation
  • Blood pressure > 150/100 mmHG
  • Grade 2 or greater proteinuria
  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: NCT00463203

Locations
Denmark
Aalborg University Hospital
Aalborg, Denmark, 9000
Rigshospitalet
Copenhagen, Denmark, 2100
Odense University Hospital
Odense, Denmark, 5000
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Ulrik Lassen, MD., PH.D. Rigshospitalet, Dept. of Oncology
  More Information

No publications provided

Responsible Party: Ulrik Lassen, Rigshospitalet
ClinicalTrials.gov Identifier: NCT00463203     History of Changes
Other Study ID Numbers: BI-Brain-01
Study First Received: April 18, 2007
Last Updated: June 27, 2011
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Rigshospitalet, Denmark:
primary malignant brain tumor
grade II glioma
meningeoma
ependymoma
Recurrence or progression after standard treatment

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Irinotecan
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on July 23, 2014