To explore if the addition of bevacizumab to temozolomide improves outcome as compared to treatment with temozolomide alone in patients with recurrent low grade and anaplastic glioma without combined 1p/19q co-deletion after prior radiotherapy and…
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
- Nervous system neoplasms malignant and unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall survival at 12 months
Secondary outcome
Ovverall survival at 24 months, progression free survival: median, at 6 and at
12 months, time to neurocognitive progression, quality of life both in the
patient and his/her proxy, toxicity
Background summary
The prognosis of patient with recurrent low grade and anaplastic glioma without
1p/19q loss after radiotherapy and/or chemotherapy is dismal. most of these
tumors recur as grade IV tumors, with a median survival after recurrence of
about 12 months. Standard of care in that situation uisualy consists of
treatment with temozolomide. This study aims to explore the the effect of the
addition of a VEGF inhibitor, bevacizumab, to the treatment with temozolomide.
Study objective
To explore if the addition of bevacizumab to temozolomide improves outcome as
compared to treatment with temozolomide alone in patients with recurrent low
grade and anaplastic glioma without combined 1p/19q co-deletion after prior
radiotherapy and or chemotherapy.
Study design
Randomized phase II study
Intervention
All patients will receive temozolomide chemotherapy which is considered
standard of care in this disease. Patients randomized to the bevacizumab arm
will receive intravenous bevacizumab once per two weeks until progression and
as long this treatment is well tolerated.
Study burden and risks
The standard of care in this situation usually consists of treatment with
temozolomide. To this treatment once every two weeks intravenous administration
of bevacizumab is added. This treatment can be complicated by side effects. As
part of the study treatment follow-up is somewhat more intensive, and quality
of life questionaires have to be filled in by the patient and his/her proxy. In
addition, neurocognitive evaluation is part of the study.
Av E Mounier 89/11
Brussel B-1200
BE
Av E Mounier 89/11
Brussel B-1200
BE
Listed location countries
Age
Inclusion criteria
- Histologically proven grade II or grade III astrocytoma, oligodendroglioma or oligoastrocytoma according to the WHO 2007 at initial diagnosis.
- Demonstrated absence of 1p/19q co-deletion according to local diagnosis.
- Availability of biological material for central review processes and translational research projects
- First recurrence after initial treatment with either radiotherapy and/or chemotherapy.
- Enhancing recurrence on MRI scan.
- For non operated patients, recurrent disease must be at least one bi-dimensionally measurable contrast enhancing lesion with clearly defined margins by MRI scan, with minimal diameters of 10 mm, visible on 2 or more axial slices 5 mm apart, based on MRI scan done within two weeks prior to start of randomisation.
- Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan.
No more than one line of chemotherapy (concurrent and adjuvant temozolomide chemotherapy is considered one line of chemotherapy)
- If given, chemotherapy must have consisted of either temozolomide or PCV, and patients must be off chemotherapy treatment for more than 6 months without progression.
- Patient may have undergone surgery for recurrence. If operated, residual and measurable disease after surgery is not required but histology must have confirmed the recurrence. Craniotomy or intracranial biopsy site must be adequately healed free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomisation.
- Absence of known hypersensitivity to any part of the Bevacizumab or Temozolomide formulations, to Chinese hamster ovary cell products or other recombinant human or humanized antibody.
- Normal hematological, renal and hepatic function functions
- Urine dipstick for proteinuria < 2+.
- Age * 18 years
- WHO Performance status 0 - 2
- Women of child bearing potential must have a negative serum or urine pregnancy test
- Female patients within one year of entering the menopause as well as males must agree to use an effective non-hormonal method of contraception during the treatment period and for at least 6 months after the last study treatment.
- Female should not be breast feeding
- Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
- written informed consent
Exclusion criteria
- Radiotherapy within the three months prior to the diagnosis of progression
- Radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven
- Current or recent (within 4 weeks before randomization) treatment with another investigational drug
- Prior treatment with Bevacizumab or other VEGF inhibitors or VEGF-Receptor signaling inhibitors
- Invasive procedures (surgical resection, open biopsy, significant traumatic injury or any other major surgery involving entry into a body cavity) within 4 weeks prior to randomization, or anticipation of the need for major surgery during the course of the study treatment.
- Core biopsy (excluding intracranial biopsy) or other minor surgical procedure within 7 days prior to randomization.
- Previous other malignancies, except for any previous malignancy which was treated with curative intent more than 5 years prior to randomisation, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of the cervix
- Any significant cardiovascular disorder
- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 m Hg)
- Any thrombotic or hemorrhagic event, including arterial or venous thrombosis * 12 months prior to randomization
- Current or recent (within 10 days of first dose of Bevacizumab) use of aspirin (> 325 mg/day) or other NSAID with anti-platelet activity or treatment with dipyramidole, ticlopidine, clopidogrel or cilostaz.
- International normalized ratio (INR) > 1.5 ULN and activated partial thromboplastin time (aPTT) >1.5 × the ULN.
- Use of full-dose anticoagulants at baseline (but prevention of thrombosis with low-dose anticoagulant is allowed)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-017422-39-NL |
| ClinicalTrials.gov | NCT01164189 |
| CCMO | NL33733.078.10 |