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

Rigshospitalet

Status and phase

Completed

Phase 2

Conditions

Glioma

Brain Neoplasms

Treatments

Drug: Irinotecan

Drug: Bevacizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT00463203

BI-Brain-01

Details and patient eligibility

About

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.

Enrollment

54 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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