GlioblastomaPhase 2NCT01100177
Study of Sunitinib Before and During Radiotherapy in Newly Diagnosed Biopsy-only Glioblastoma Patients
A Phase 2 study testing Sunitinib and Radiation in people with Glioblastoma, run by Grupo Español de Investigación en Neurooncología at 1 site in Spain.
Trial summary
Sunitinib seems to be a promising treatment for the objective of this proposal: to evaluate the clinical activity of Sunitinib as first line therapy in patients who have measurable disease and to evaluate the safety of Sunitinib with radiation therapy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Sunitinib and Radiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSpain
- Study dates
- Jun 2009to Jan 2012
- Phase
- Phase 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with glioblastoma, non resectable, who have only a biopsy as surgical treatment.
- Measurable disease and with contrast capture of 2cm
- Stable doses of DXM during the week before the inclusion
- Performance status 0-1-2
- Age < 75 years
- MMS > 25/30
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- Barthel index > 50%
- Surgical incision must have healed before the inclusion
- Basal MRI done 3 weeks at the most before the beginning of the treatment which has specified conditions at the protocol.
- FEVI > 50%
- Suitable medullar reserve (neutrophils _2000x109/L, platelets _ 100x109/L, Haemoglobin _ 10 g/dl.)
- Not previous chemotherapy or radiation treatment.
- Creatinin < 1,5 times the superior standard limit of the laboratory in charged of the analysis.
- Serum Bilirubin < 1, 5/ULN, SGOT y SGPT _ 2,5 times the superior standard limit of the laboratory in charged of the analysis. Serum alkaline phosphatases < 3/ULN.
- Effective contraception method in patients and their couple.
- Informed consent.
Who cannot join
- Previous radiation or chemotherapy for the glioma´s treatment.
- Less than 5 years time from any previous infiltrant neoplasia
- Serious Cerebral haemorrhage after biopsy
- Anticomital treatment inducting / inhibiting the CYP3A4 enzyme: fenitoin, carbamacepzin, phenobarbitone or other drugs that interact with sunitinib metabolism and that could not be replaced by another drug without interactions with Sunitinib.
- Pregnancy or lactation.
- Active or not controlled cardiovascular disease such as hypertension, angor instable, cardiac congestive failure IInd degree (NYHA), cardiac arrhythmia, previous myocardium heart attack, up to 1 year before the randomization
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- Currently treatment established with therapeutic doses of derivated anticoagulants of coumarin (coumarin, warfarin) or a week before the beginning of sunitinib. The administration of heparins of low molecular weight for TVP's control is allowed
- Patient with TVP
- HTA with higher values than 150/100 and not controllable with antihypertensive standard drugs
- Not healed scars, sores or bone fractures
- Hemorrhagic diathesis or coagulate illnesses
Trial locations and contacts
1 site in 1 country.
Spain1 site
Grupo Español de Investigacion en Neurooncologia
Madrid, Madrid, 28001
About this study
Official title: An Open Label Non- Randomized Multicentric Phase II Study of Sunitinib Before and During Radiotherapy in Newly Diagnosed Biopsy-only Glioblastoma Patients
Sunitinib seems to be a promising treatment for the objective of this proposal: to evaluate the clinical activity of Sunitinib as first line therapy in patients who have measurable disease and to evaluate the safety of Sunitinib with radiation therapy.
Read the detailed description
Sunitinib (SU 11248) is a small molecule with good oral bioavailability that inhibits multiple receptor tyrosine kinases (RTKs) expressed on diverse tumour cells: VEGFR, PDGFR, KIT, FLT3 and endothelium, pericytes, and stroma VEGFR, PDGFR. It has the potential to inhibit directly the growth of multiple tumour types by the inhibition of multiple targets and to act negatively on antiangiogenesis.
Glioblastoma (GB) is the most frequent brain tumour. Standard treatment after surgical resection is radiation therapy with Temozolomide. But patients who can afford only a biopsy of their lesion due to the location in eloquent areas of their tumour or multifocality, don't get benefit from such treatment and their median survival is in the best case of only 9 months. These patients constitute 30% of Glioblastomas. Clinical trials in this setting are required as patients should be treated immediately after the biopsy to prevent neurological deterioration.
These patients are ideal to test new promising therapies. Their survival is similar to recurrent patients. The evaluation of response is easier as it's possible to avoid the confounding post-surgical changes that interfere with the evaluation of treatment efficacy in terms of tumour size reduction.. Furthermore, neo adjuvant treatment before radiotherapy has shown not to worsen their survival.
Glioblastoma is a tumour rich in molecular abnormalities. PDGFRs are important in growth signalling pathways and neoangiogenesis of gliomas. PDGF ligands and PDGFR-alfa are expressed in most human gliomas, while PDGFR-beta is expressed in glioma cells and tumor endothelial cells, PDFGR-α is expressed in most human gliomas. Imatinib mesylate exhibited antiglioma activity in preclinical studies, sensitizes glioma cells to radiation injury, and combined with hydroxyurea has shown promising results in the recurrent setting.
Moreover gliomas are among the most angiogenic cancers. VEGF/VEGFR-2 is the most prominent angiogenic signalling pathway. Its inhibition either by a neutralizing anti-VEGF antibody, anti-sense VEGF constructs, expression of a dominant-negative mutant form of VEGFR-2 (a specific small molecule inhibitor of the VEGFR-2 tyrosine kinase) or neutralizing anti-VEGFR-2 antibody has resulted in suppression of experimental malignant glioma growth. VEGF has been the focus in the development of glioma-targeted therapies. Recently Bevacizumab has shown to be active in phase II studies.
For these reasons, Sunitinib seems to be a promising treatment fo The objective of this proposal is to evaluate the clinical activity of Sunitinib as first line therapy in patients who have measurable disease and to evaluate the safety of Sunitinib with radiation therapy.
- Conditions
- Glioblastoma
- Keywords
- Patients with non resectable Glioblastoma who have only a, biopsy as surgical treatment
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Sunitinib 37.5mg/m2/d
RadiationRadiation
Radiation therapy (60Gy) 2 Gy per day during 30 days
| Study group | Role | What they receive |
|---|---|---|
| Sunitinib plus radiothery | Experimental | * Sunitinib at doses of 37.5mg/m2/daily in a continuous dosing during 8 weeks.
* After evaluation of efficacy, they will receive Sunitinib 37.5 mg/d and treatment with Radiation therapy (total dose 60 Gy).
* After radiation therapy, Sunitinib al 37.5 mg/d will be continued until progression. Receives: Drug: Sunitinib; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate to Sunitinib therapy
Clinical activity in terms of clinical response (RANO criteria) after 2, 4 weeks cycles of Sunitinib treatment.
Measured: 8 weeks after treatment
Secondary outcomes (4)
Safety of Sunitinib with Radiation therapy
Percentage of patients without neurological damage after the first 14 weeks of the treatment
Measured: 14 weeks
Assess the number of patients without neurological deterioration before radiation
Measured: 8 weeks
Evaluation of progression free survival
After radiation therapy, Sunitinib will be continued until progression. (Evaluation of progression free survival)
Measured: participants are followed until progression
Overall survival
Measured: participants are followed until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2010 (estimated)
- Study startJun 2009
- Primary completionDec 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Español de Investigación en Neurooncología
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carmen Balaña, Coordiantor, Study chair, Hospital Germans Trias i Pujol, Badalona, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01100177
- Sponsor's protocol ID
- GENOM-008
- Status last verified
- Mar 2013
- First submitted
- 1 Apr 2010
- Last updated
- 11 Mar 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Non- Randomized Multicentric Phase II Study of Sunitinib Before and During Radiotherapy in Newly Diagnosed Biopsy-only Glioblastoma Patients
- ClinicalTrials.gov ID
- NCT01100177
- Acronym / sponsor ID
- GENOM-008
- Conditions
- Glioblastoma
- Keywords
- Patients with non resectable Glioblastoma who have only a, biopsy as surgical treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Grupo Español de Investigación en NeurooncologíaUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 8 Apr 2010 (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.
Sunitinib seems to be a promising treatment for the objective of this proposal: to evaluate the clinical activity of Sunitinib as first line therapy in patients who have measurable disease and to evaluate the safety of Sunitinib with radiation therapy.
Detailed description
Sunitinib (SU 11248) is a small molecule with good oral bioavailability that inhibits multiple receptor tyrosine kinases (RTKs) expressed on diverse tumour cells: VEGFR, PDGFR, KIT, FLT3 and endothelium, pericytes, and stroma VEGFR, PDGFR. It has the potential to inhibit directly the growth of multiple tumour types by the inhibition of multiple targets and to act negatively on antiangiogenesis.
Glioblastoma (GB) is the most frequent brain tumour. Standard treatment after surgical resection is radiation therapy with Temozolomide. But patients who can afford only a biopsy of their lesion due to the location in eloquent areas of their tumour or multifocality, don't get benefit from such treatment and their median survival is in the best case of only 9 months. These patients constitute 30% of Glioblastomas. Clinical trials in this setting are required as patients should be treated immediately after the biopsy to prevent neurological deterioration.
These patients are ideal to test new promising therapies. Their survival is similar to recurrent patients. The evaluation of response is easier as it's possible to avoid the confounding post-surgical changes that interfere with the evaluation of treatment efficacy in terms of tumour size reduction.. Furthermore, neo adjuvant treatment before radiotherapy has shown not to worsen their survival.
Glioblastoma is a tumour rich in molecular abnormalities. PDGFRs are important in growth signalling pathways and neoangiogenesis of gliomas. PDGF ligands and PDGFR-alfa are expressed in most human gliomas, while PDGFR-beta is expressed in glioma cells and tumor endothelial cells, PDFGR-α is expressed in most human gliomas. Imatinib mesylate exhibited antiglioma activity in preclinical studies, sensitizes glioma cells to radiation injury, and combined with hydroxyurea has shown promising results in the recurrent setting.
Moreover gliomas are among the most angiogenic cancers. VEGF/VEGFR-2 is the most prominent angiogenic signalling pathway. Its inhibition either by a neutralizing anti-VEGF antibody, anti-sense VEGF constructs, expression of a dominant-negative mutant form of VEGFR-2 (a specific small molecule inhibitor of the VEGFR-2 tyrosine kinase) or neutralizing anti-VEGFR-2 antibody has resulted in suppression of experimental malignant glioma growth. VEGF has been the focus in the development of glioma-targeted therapies. Recently Bevacizumab has shown to be active in phase II studies.
For these reasons, Sunitinib seems to be a promising treatment fo The objective of this proposal is to evaluate the clinical activity of Sunitinib as first line therapy in patients who have measurable disease and to evaluate the safety of Sunitinib with radiation therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib plus radiothery | Experimental | Drug: Sunitinib, Radiation: Radiation* Sunitinib at doses of 37.5mg/m2/daily in a continuous dosing during 8 weeks. * After evaluation of efficacy, they will receive Sunitinib 37.5 mg/d and treatment with Radiation therapy (total dose 60 Gy). * After radiation therapy, Sunitinib al 37.5 mg/d will be continued until progression. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with glioblastoma, non resectable, who have only a biopsy as surgical treatment.
- Measurable disease and with contrast capture of 2cm
- Stable doses of DXM during the week before the inclusion
- Performance status 0-1-2
- Age < 75 years
Key exclusion criteria (11 listed)
- Previous radiation or chemotherapy for the glioma´s treatment.
- Less than 5 years time from any previous infiltrant neoplasia
- Serious Cerebral haemorrhage after biopsy
- Anticomital treatment inducting / inhibiting the CYP3A4 enzyme: fenitoin, carbamacepzin, phenobarbitone or other drugs that interact with sunitinib metabolism and that could not be replaced by another drug without interactions with Sunitinib.
- Pregnancy or lactation.
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 |
|---|---|---|
| SunitinibSunitinib 37.5mg/m2/d | Drug | Sunitinib plus radiothery |
| RadiationRadiation therapy (60Gy) 2 Gy per day during 30 days | Radiation | Sunitinib plus radiothery |
Primary outcome
Objective response rate to Sunitinib therapy
Time frame: 8 weeks after treatment
Clinical activity in terms of clinical response (RANO criteria) after 2, 4 weeks cycles of Sunitinib treatment.
4 secondary outcomes
Safety of Sunitinib with Radiation therapy
Time frame: 14 weeks
Assess the number of patients without neurological deterioration before radiation
Time frame: 8 weeks
Evaluation of progression free survival
Time frame: participants are followed until progression
Overall survival
Time frame: participants are followed until death
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 11 Mar 2013.
- Related InfoLink provided by the sponsor.
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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.
Carmen Balaña, Coordiantor study chair
Hospital Germans Trias i Pujol, Badalona, Spain
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sunitinib and Radiation in people with Glioblastoma, run by Grupo Español de Investigación en Neurooncología at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. 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 11 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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 phase mean?
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?
Objective response rate to Sunitinib therapy (time frame: 8 weeks after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Mar 2013.