GlioblastomasPhase 2NCT01102595
Neo-adjuvant Treatment With Temozolomide and Bevacizumab Previous to Temozolomide Plus Radiation Plus Bevacizumab Therapy in Unresectable Glioblastoma
A Phase 2 study testing Temozolomide, Bevacizumab and Standard radiation therapy in people with Glioblastomas, run by Grupo Español de Investigación en Neurooncología at 1 site in Spain.
Trial summary
In the last 20 years, only temozolomide has obtained indication for the treatment of High-grade glioma (HGG). Temozolomide during and later radiation therapy has doubled one year survival and is the standard treatment for glioblastoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Glioblastomas
- What is being tested?
- Temozolomide, Bevacizumab and Standard radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteSpain
- Study dates
- Dec 2009to Dec 2014
- 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, biopsy only. Accepting a craniotomy with resection attempted if an RMN within a period of about 72 hours to confirm that the resection was less than 25% of the tumor and fulfill criterion
- Measurable disease and contrast uptake ≥ 3 cm in one of its diameters.
- Stable doses of dexamethasone during the week prior to inclusion.
- Performance Status ≤ 2.
- Age ≤ 75 years.
- MiniMental Status> 25/30.
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- Bartel index > 50%.
- The surgical incision should be healed prior to randomization. The treatment can be started at 3 weeks of a simple stereotactic biopsy or 4 weeks in case of open biopsy (craniotomy).
- Maximum baseline MRI performed 4 weeks before starting treatment (acceptance of the MRI done for neuronavegation biopsy as baseline).
- Adequate bone marrow reserve: neutrophils>2000x109/L, platelets>100x109/L, hemoglobin≥106g/dl.
- Not received prior treatment with chemotherapy or radiation.
- Adequate renal function: Creatinine <1.5 ULN of the laboratory performing the analysis.
- Adequate liver function: Serum bilirubin <1.5/ULN SGOT, SGPT<2.5ULN. Serum alkaline phosphatase<3/ULN.
- Absence of proteinuria.
- Effective method of contraception for patients and their partners.
- Written informed consent
- Collecting material for a double histological confirmation of diagnosis.
Who cannot join
- Prior radiotherapy or chemotherapy for the treatment of glioma.
- Less than 5 years prior to any invasive neoplasia. Accepted carcinoma in situ of cervix carcinoma or cutaneous vasocelular.
- Cerebral hemorrhage after biopsy.
- Pregnancy or lactation.
- Clinically significant cardiovascular disease: - Myocardial infarction or unstable angina (≤ 6 months before randomization) - Congestive heart failure (CHF) class ≥ II NYHA, New York Heart Association. - Cardiac Arrhythmia uncontrolled despite medication (may include patients with atrial fibrillation often controlled). - Peripheral vascular disease ≥ grade 3 (ie, symptomatic and interfering with everyday activities or specifying repairs or review).
- Continued use of aspirin> 325 mg / day, currently or recently (within the 10 days prior to randomization).
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- Currently established treatment with therapeutic doses of anticoagulants Coumarin derivatives (courmarina, warfarin) or a week before starting treatment. It allows the administration of heparin for control of Deep Vein Thrombosis (DVT)
- Patients with PTSD and patients with inflammatory bowel disease, with risk of perforation.
- HT with values above 150 mmHg systolic pressure of 100 mmHg and diastolic tension is not controllable with standard antihypertensive drugs.
- Not healed scars, ulcers or recent bone fracture.
- Bleeding diathesis or coagulopathy.
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: A Phase II Open Label Randomised Multicentric Study in Patients With Unresectable Glioblastoma Using Neo-adjuvant Treatment With Two Cycles of Temozolomide Previous Temozolomide Plus Radiation Therapy and Adjuvant Temozolomide vs. Neo-adjuvant Treatment With Two Cycles of Temozolomide Plus Bevacizumab Previous Temozolomide, Bevacizumab and Radiation Therapy and Adjuvant Temozolomide.
In the last 20 years, only temozolomide has obtained indication for the treatment of High-grade glioma (HGG). Temozolomide during and later radiation therapy has doubled one year survival and is the standard treatment for glioblastoma. But 30% of glioblastomas receive only a biopsy as they can't be resected and don't get benefit from this treatment. They and should be treated immediately after the biopsy to prevent neurological deterioration but in spite of this approach they often deteriorate neurologically during radiotherapy. . An effective pre-radiation treatment should improve their prognosis and allow them to complete concomitant radiotherapy and temozolomide treatment. Bevacizumab in recurrent HGG displays 63% of objective responses when combined with irinotecan. But irinotecan is not the most active treatment in this disease.
We propose a phase II, two arms, open label, randomized, multicentric study with 2 cycles of temozolomide before radiation therapy and concomitant temozolomide, in patients with glioblastoma and 'biopsy-only'. Bevacizumab will be added to one arm.
- Conditions
- Glioblastomas
- Being tested
- Temozolomide, Bevacizumab, Standard radiation therapy
- Keywords
- Unresectable/inoperable glioblastomas
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
- Temozolomide 85 mg/m2/d x 21 days every 28 days for 2 cycles.
- Temozolomide 75 mg/m2/d x 42-49 days
- Temozolomide 150 - 200 mg/m2 d1-d5 q 28d for 6 cycles.
BevacizumabDrug
- 2 cycles + bevacizumab 10 mg/kg every 15 days each two cycles.
- Bevacizumab 10 mg/kg every 15 days, three dosis.
Standard radiation therapyRadiation
42-49 days with standard radiation therapy (60 Gy): 2 Gy per day.
| Study group | Role | What they receive |
|---|---|---|
| 1: Temozolomide plus Radiation | Experimental | Group 1:
Neoadjuvant phase: Temozolomide 85 mg/m2/d x 21 days every 28 days for 2 cycles.
Adjuvant phase: Temozolomide 75 mg/m2/d x 42-49 days with standard radiation therapy (60 Gy).
Maintenance phase: Temozolomide 150 - 200 mg/m2 d1-d5 q 28d for 6 cycles. Receives: Drug: Temozolomide; Radiation: Standard radiation therapy |
| 2: Temozolomide plus Radiation plus Bevacizumab | Experimental | Neoadjuvant phase: Temozolomide 85 mg/m2/d x 21 days every 28 days for 2 cycles + bevacizumab 10 mg/kg every 15 days.
Adjuvant phase: Temozolomide 75 mg/m2/d x 42-49 days with standard radiation therapy (60 Gy) + bevacizumab 10 mg/kg every 15 days.
Maintenance phase: Temozolomide 150 - 200 mg/m2 d1-d5 q 28d for 6 cycles. Receives: Drug: Temozolomide; Drug: Bevacizumab; Radiation: Standard radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
To determine differences in clinical activity in terms of objective response after 2 cycles of 4 weeks in both treatment arms in inoperable patients with glioblastoma (RANO criteria)
Measured: Until the first 9 weeks of treatment
Secondary outcomes (5)
Percentage of patients who finish treatment
Measured: 41 weeks
Progression-free survival
Measured: the participants will be followed until disease progression by RANO criteria
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Assess the toxicity of the combination of the treatment.
Temozolamide+bevacizumab+radiation Temozolamide+radiation
After the inclusion of the first 10 patients treated with bevacizumab arm (arm 2)the inclusion will be temporarily interrupted until the last of these patients completed concomitant treatment (radiation, temozolomide, bevacizumab) to check the safety of treatment with analysis of adverse effects and toxicity.
following the NCIC 3.0 criteria.
Measured: 21 weeks
Percentage of patients without neurological deterioration before radiation therapy.
Measured: 8 weeks
Overall survival
Measured: Until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2010 (estimated)
- Study startDec 2009
- Primary completionOct 2013
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomasStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Español de Investigación en Neurooncología
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01102595
- Sponsor's protocol ID
- GENOM-009
- Status last verified
- Aug 2015
- First submitted
- 1 Apr 2010
- Last updated
- 26 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open Label Randomised Multicentric Study in Patients With Unresectable Glioblastoma Using Neo-adjuvant Treatment With Two Cycles of Temozolomide Previous Temozolomide Plus Radiation Therapy and Adjuvant Temozolomide vs. Neo-adjuvant Treatment With Two Cycles of Temozolomide Plus Bevacizumab Previous Temozolomide, Bevacizumab and Radiation Therapy and Adjuvant Temozolomide.
- ClinicalTrials.gov ID
- NCT01102595
- Acronym / sponsor ID
- GENOM-009
- Conditions
- Glioblastomas
- Keywords
- Unresectable/inoperable glioblastomas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Grupo Español de Investigación en NeurooncologíaUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Oct 2013 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 13 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.
In the last 20 years, only temozolomide has obtained indication for the treatment of High-grade glioma (HGG). Temozolomide during and later radiation therapy has doubled one year survival and is the standard treatment for glioblastoma. But 30% of glioblastomas receive only a biopsy as they can't be resected and don't get benefit from this treatment. They and should be treated immediately after the biopsy to prevent neurological deterioration but in spite of this approach they often deteriorate neurologically during radiotherapy. . An effective pre-radiation treatment should improve their prognosis and allow them to complete concomitant radiotherapy and temozolomide treatment. Bevacizumab in recurrent HGG displays 63% of objective responses when combined with irinotecan. But irinotecan is not the most active treatment in this disease.
We propose a phase II, two arms, open label, randomized, multicentric study with 2 cycles of temozolomide before radiation therapy and concomitant temozolomide, in patients with glioblastoma and 'biopsy-only'. Bevacizumab will be added to one arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: Temozolomide plus Radiation | Experimental | Drug: Temozolomide, Radiation: Standard radiation therapyGroup 1: Neoadjuvant phase: Temozolomide 85 mg/m2/d x 21 days every 28 days for 2 cycles. Adjuvant phase: Temozolomide 75 mg/m2/d x 42-49 days with standard radiation therapy (60 Gy). Maintenance phase: Temozolomide 150 - 200 mg/m2 d1-d5 q 28d for 6 cycles. |
| 2: Temozolomide plus Radiation plus Bevacizumab | Experimental | Drug: Temozolomide, Drug: Bevacizumab, Radiation: Standard radiation therapyNeoadjuvant phase: Temozolomide 85 mg/m2/d x 21 days every 28 days for 2 cycles + bevacizumab 10 mg/kg every 15 days. Adjuvant phase: Temozolomide 75 mg/m2/d x 42-49 days with standard radiation therapy (60 Gy) + bevacizumab 10 mg/kg every 15 days. Maintenance phase: Temozolomide 150 - 200 mg/m2 d1-d5 q 28d for 6 cycles. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients with glioblastoma, non-resectable, biopsy only. Accepting a craniotomy with resection attempted if an RMN within a period of about 72 hours to confirm that the resection was less than 25% of the tumor and fulfill criterion
- Measurable disease and contrast uptake ≥ 3 cm in one of its diameters.
- Stable doses of dexamethasone during the week prior to inclusion.
- Performance Status ≤ 2.
- Age ≤ 75 years.
Key exclusion criteria (11 listed)
- Prior radiotherapy or chemotherapy for the treatment of glioma.
- Less than 5 years prior to any invasive neoplasia. Accepted carcinoma in situ of cervix carcinoma or cutaneous vasocelular.
- Cerebral hemorrhage after biopsy.
- Pregnancy or lactation.
- Clinically significant cardiovascular disease: - Myocardial infarction or unstable angina (≤ 6 months before randomization) - Congestive heart failure (CHF) class ≥ II NYHA, New York Heart Association. - Cardiac Arrhythmia uncontrolled despite medication (may include patients with atrial fibrillation often controlled). - Peripheral vascular disease ≥ grade 3 (ie, symptomatic and interfering with everyday activities or specifying repairs or review).
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* Temozolomide 85 mg/m2/d x 21 days every 28 days for 2 cycles. * Temozolomide 75 mg/m2/d x 42-49 days * Temozolomide 150 - 200 mg/m2 d1-d5 q 28d for 6 cycles. | Drug | 1: Temozolomide plus Radiation, 2: Temozolomide plus Radiation plus Bevacizumab |
| Bevacizumab* 2 cycles + bevacizumab 10 mg/kg every 15 days each two cycles. * Bevacizumab 10 mg/kg every 15 days, three dosis. | Drug | 2: Temozolomide plus Radiation plus Bevacizumab |
| Standard radiation therapy42-49 days with standard radiation therapy (60 Gy): 2 Gy per day. | Radiation | 1: Temozolomide plus Radiation, 2: Temozolomide plus Radiation plus Bevacizumab |
Primary outcome
Response Rate
Time frame: Until the first 9 weeks of treatment
To determine differences in clinical activity in terms of objective response after 2 cycles of 4 weeks in both treatment arms in inoperable patients with glioblastoma (RANO criteria)
5 secondary outcomes
Percentage of patients who finish treatment
Time frame: 41 weeks
Progression-free survival
Time frame: the participants will be followed until disease progression by RANO criteria
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 21 weeks
Percentage of patients without neurological deterioration before radiation therapy.
Time frame: 8 weeks
Overall survival
Time frame: 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 26 Aug 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Temozolomide, Bevacizumab and Standard radiation therapy in people with Glioblastomas, 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 17 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 26 Aug 2015. 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?
Response Rate (time frame: Until the first 9 weeks of 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 26 Aug 2015.