Brain and Central Nervous System TumorsPhase 1/2NCT00128700
Temozolomide and Radiation Therapy With or Without Vatalanib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
A Phase 1/2 study testing temozolomide, vatalanib and adjuvant therapy in people with Brain and Central Nervous System Tumors, run by European Organisation for Research and Treatment of Cancer - EORTC at 5 sites in 5 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- temozolomide, vatalanib and adjuvant therapy
- Type of treatment
- Surgery or procedure
- How many people
- 20 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Jun 2005to Nov 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed glioblastoma multiforme
- Newly diagnosed disease
- Deemed to be amenable to concurrent and adjuvant temozolomide treatment by the principal investigator
PATIENT CHARACTERISTICS:
Age
- 18 to 69
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin < 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase < 2.5 times ULN
- ALT and AST < 2.5 times ULN
Renal
- Creatinine ≤ 1.7 mg/dL
Cardiovascular
- Cardiac function clinically normal
- 12-lead ECG normal
- No ischemic heart disease within the past 6 months
- No uncontrolled cardiac arrhythmia
- No uncontrolled hypertension
- No history of stroke
- No history of congenital long QT syndrome
- QTc interval ≤ 450 msec for males or ≤ 470 msec for females by 12-lead ECG
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy except adequately treated basal cell or squamous cell skin cancer or cone biopsied carcinoma in situ of the cervix
- No active uncontrolled infection
- No other unstable systemic disease
- No psychological, familial, sociological, or geographical condition that would preclude study compliance or follow-up schedule
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior anti-vascular endothelial growth factor therapy
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Concurrent corticosteroids allowed provided the patient is on stable or decreasing doses for ≥ 2 weeks before study entry
Radiotherapy
- No prior radiotherapy
Surgery
- More than 8 days, but < 6 weeks, since prior surgery or biopsy
Other
- No prior randomization on this study
- No concurrent warfarin, warfarin-derived drugs, or similar anticoagulants
- No other concurrent anticancer therapy
- No other concurrent investigational agents
- No concurrent enzyme inducing antiepileptic drugs, including any of the following:
- Carbamazepine
- Fosphenytoin
- Oxcarbazepine
- Phenobarbital
- Phenytoin
- Primidone
- No concurrent grapefruit or grapefruit juice
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Netherlands1 site
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Rotterdam, 3075 EA
Switzerland1 site
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011
About this study
Official title: Phase I/II Study on Concomitant and Adjuvant Temozolomide and Radiotherapy With or Without PTK787/ZK222584 in Newly Diagnosed GBM
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Vatalanib may stop the growth of tumor cells by blocking blood flow to the tumor. Giving temozolomide and radiation therapy together with vatalanib may kill more tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of vatalanib when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of vatalanib when given in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme. (Phase I)
- Determine the safety and tolerability of this regimen in these patients. (Phase I)
- Determine the 6-month progression-free survival of patients treated with chemoradiotherapy comprising temozolomide and radiotherapy with or without vatalanib followed by adjuvant therapy comprising temozolomide and vatalanib or temozolomide alone with or without maintenance therapy comprising vatalanib alone. (Phase II)
Secondary
- Determine 12-month overall survival of patients treated with these regimens. (Phase II)
- Determine the toxicity profile of these regimens in these patients. (Phase II)
- Correlate expression of angiogenesis and hypoxia markers and MGMT methylation status with clinical outcome in patients treated with these regimens.
OUTLINE: This is a phase I, multicenter, open-label, non-randomized, dose-escalation study of vatalanib followed by a phase II, randomized, controlled study. Patients enrolled in the phase II portion of the study are stratified according to participating center, age (< 50 years vs ≥ 50 years), corticosteroid intake (yes vs no), and mini-mental status evaluation score (< 27 vs 27-29 vs 30).
- Phase I:
- Chemoradiotherapy: Patients receive oral temozolomide once daily for 6-7 weeks and oral vatalanib once daily for 6 weeks. Patients also undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients continue to receive oral vatalanib twice daily.
Cohorts of 3-6 patients receive escalating doses of vatalanib during chemoradiotherapy until the maximum tolerated dose is determined (MTD). The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
- Adjuvant therapy: Patients receive oral temozolomide once daily on days 1-5 and oral vatalanib twice daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance therapy.
- Maintenance therapy: Patients continue to receive oral vatalanib twice daily in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients are randomized to 1 of 3 treatment arms.
- Arm I:
- Chemoradiotherapy: Patients receive oral temozolomide once daily for 6-7 weeks and undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy.
- Adjuvant therapy: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II:
- Chemoradiotherapy: Patients receive temozolomide and undergo radiotherapy as in arm I. Patients also receive vatalanib twice daily for 6 weeks at the MTD determined in phase I. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients continue to receive oral vatalanib twice daily.
- Adjuvant therapy: Patients receive temozolomide and vatalanib as in phase I adjuvant therapy. Patients then proceed to maintenance therapy.
- Maintenance therapy: Patients continue to receive vatalanib as in phase I maintenance therapy.
- Arm III:
- Chemoradiotherapy: Patients receive temozolomide and undergo radiotherapy as in arm I. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients receive oral vatalanib twice daily.
- Adjuvant therapy: Patients receive temozolomide and vatalanib as in phase I adjuvant therapy. Patients then proceed to maintenance therapy.
- Maintenance therapy: Patients continue to receive vatalanib as in phase I maintenance therapy.
After completion of study treatment, patients are followed every 3 months for survival.
PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 201 patients (67 per treatment arm) will be accrued for the phase II portion of this study.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- temozolomide, vatalanib, adjuvant therapy, radiation therapy
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temozolomideDrug
vatalanibDrug
adjuvant therapyProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity and maximum tolerated dose of vatalanib as determined by CTCAE v3.0 during phase I
Progression-free survival at 6 months during phase II
Secondary outcomes (3)
Severe toxic events as assessed by CTCAE v3.0 at weeks 3 and 6 (concomitant treatment), weeks 2 and 4 after radiotherapy, before each course of adjuvant treatment, monthly during maintenance treatment, and every 3 months during follow-up in phase II
Overall survival at 1 year during phase II
Correlation of angiogenesis and hypoxia markers expression and O-6-methylguanine DNA methyltransferase (MGMT) methylation status with clinical outcome during phase II
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2005 (estimated)
- Study startJun 2005
- Primary completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Alba A. Brandes, MD, Study chair, Azienda Ospedaliera di Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00128700
- Sponsor's protocol ID
- EORTC-26041-22041
- Other IDs
- EORTC-26041, EORTC-22041, EUDRACT-2004-003896-35
- Status last verified
- Sep 2012
- First submitted
- 8 Aug 2005
- Last updated
- 24 Sep 2012
- Results posted
- No
Publications
Brandes AA, Stupp R, Hau P, Lacombe D, Gorlia T, Tosoni A, Mirimanoff RO, Kros JM, van den Bent MJ. EORTC study 26041-22041: phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma. Eur J Cancer. 2010 Jan;46(2):348-54. doi: 10.1016/j.ejca.2009.10.029. Epub 2009 Nov 27.
PubMed 19945857
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study on Concomitant and Adjuvant Temozolomide and Radiotherapy With or Without PTK787/ZK222584 in Newly Diagnosed GBM
- ClinicalTrials.gov ID
- NCT00128700
- Acronym / sponsor ID
- EORTC-26041-22041
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Jun 2005
- Primary completion
- Nov 2007 (actual)
- First posted
- 10 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Vatalanib may stop the growth of tumor cells by blocking blood flow to the tumor. Giving temozolomide and radiation therapy together with vatalanib may kill more tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of vatalanib when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of vatalanib when given in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme. (Phase I)
- Determine the safety and tolerability of this regimen in these patients. (Phase I)
- Determine the 6-month progression-free survival of patients treated with chemoradiotherapy comprising temozolomide and radiotherapy with or without vatalanib followed by adjuvant therapy comprising temozolomide and vatalanib or temozolomide alone with or without maintenance therapy comprising vatalanib alone. (Phase II)
Secondary
- Determine 12-month overall survival of patients treated with these regimens. (Phase II)
- Determine the toxicity profile of these regimens in these patients. (Phase II)
- Correlate expression of angiogenesis and hypoxia markers and MGMT methylation status with clinical outcome in patients treated with these regimens.
OUTLINE: This is a phase I, multicenter, open-label, non-randomized, dose-escalation study of vatalanib followed by a phase II, randomized, controlled study. Patients enrolled in the phase II portion of the study are stratified according to participating center, age (< 50 years vs ≥ 50 years), corticosteroid intake (yes vs no), and mini-mental status evaluation score (< 27 vs 27-29 vs 30).
- Phase I:
- Chemoradiotherapy: Patients receive oral temozolomide once daily for 6-7 weeks and oral vatalanib once daily for 6 weeks. Patients also undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients continue to receive oral vatalanib twice daily.
Cohorts of 3-6 patients receive escalating doses of vatalanib during chemoradiotherapy until the maximum tolerated dose is determined (MTD). The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
- Adjuvant therapy: Patients receive oral temozolomide once daily on days 1-5 and oral vatalanib twice daily on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance therapy.
- Maintenance therapy: Patients continue to receive oral vatalanib twice daily in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients are randomized to 1 of 3 treatment arms.
- Arm I:
- Chemoradiotherapy: Patients receive oral temozolomide once daily for 6-7 weeks and undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy.
- Adjuvant therapy: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II:
- Chemoradiotherapy: Patients receive temozolomide and undergo radiotherapy as in arm I. Patients also receive vatalanib twice daily for 6 weeks at the MTD determined in phase I. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients continue to receive oral vatalanib twice daily.
- Adjuvant therapy: Patients receive temozolomide and vatalanib as in phase I adjuvant therapy. Patients then proceed to maintenance therapy.
- Maintenance therapy: Patients continue to receive vatalanib as in phase I maintenance therapy.
- Arm III:
- Chemoradiotherapy: Patients receive temozolomide and undergo radiotherapy as in arm I. Four weeks after the completion of chemoradiotherapy, patients proceed to adjuvant therapy. During the 4-week period between chemoradiotherapy and adjuvant therapy, patients receive oral vatalanib twice daily.
- Adjuvant therapy: Patients receive temozolomide and vatalanib as in phase I adjuvant therapy. Patients then proceed to maintenance therapy.
- Maintenance therapy: Patients continue to receive vatalanib as in phase I maintenance therapy.
After completion of study treatment, patients are followed every 3 months for survival.
PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 201 patients (67 per treatment arm) will be accrued for the phase II portion of this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| temozolomide | Drug | – |
| vatalanib | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Dose-limiting toxicity and maximum tolerated dose of vatalanib as determined by CTCAE v3.0 during phase I
Progression-free survival at 6 months during phase II
3 secondary outcomes
Severe toxic events as assessed by CTCAE v3.0 at weeks 3 and 6 (concomitant treatment), weeks 2 and 4 after radiotherapy, before each course of adjuvant treatment, monthly during maintenance treatment, and every 3 months during follow-up in phase II
Overall survival at 1 year during phase II
Correlation of angiogenesis and hypoxia markers expression and O-6-methylguanine DNA methyltransferase (MGMT) methylation status with clinical outcome during phase II
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2012.
- Results publication: PubMed 19945857Brandes AA, Stupp R, Hau P, Lacombe D, Gorlia T, Tosoni A, Mirimanoff RO, Kros JM, van den Bent MJ. EORTC study 26041-22041: phase I/II study on concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) with PTK787/ZK222584 (PTK/ZK) in newly diagnosed glioblastoma. Eur J Cancer. 2010 Jan;46(2):348-54. doi: 10.1016/j.ejca.2009.10.029. Epub 2009 Nov 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alba A. Brandes, MD study chair
Azienda Ospedaliera di Padova
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing temozolomide, vatalanib and adjuvant therapy in people with Brain and Central Nervous System Tumors, run by European Organisation for Research and Treatment of Cancer - EORTC at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium, Germany, Italy, Netherlands, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity and maximum tolerated dose of vatalanib as determined by CTCAE v3.0 during phase I. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00128700, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2012.