Naive Unresectable GlioblastomaPhase 2TemAvIrNCT01022918
Evaluation of the Irinotecan/Bevacizumab Association for Naive Unresectable Glioblastoma
A Phase 2 study testing Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures) and Temodal/radiotherapy in people with Naive Unresectable Glioblastoma, run by Centre Georges Francois Leclerc at 1 site in France.
Trial summary
Treatment of glioblastoma (GBM) is based on surgery when possible, and chemoradiation with temozolomide, which became a standard since the EORTC study (Stupp, 2005). However, the prognosis of unresectable GBM remains poor despite chemoradiation with an estimated 10 month median survival, in the range of the comparable… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Naive Unresectable Glioblastoma
- What is being tested?
- Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures) and Temodal/radiotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2009to Jan 2011
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All the eligibility criteria must be met before registration :
- delay upper or equal to 14 days from stereotaxic biopsy and 28 days from surgical biopsy
- Histopathologically proven diagnosis of glioblastoma (WHO grade IV astrocytoma)
- Patient belonging to the RPA V class or associated
- only supratentorial glioblastoma
- Diagnosis must be obtained by a stereotactic or surgical biopsy
Show all 19Show fewer
- Age between 18 and 70
- A contrast-enhanced MRI must be performed within 28 days prior to study registration
- Total or partial surgical resection deemed as not possible by a neurosurgeon
- Karnofsky Index (KI) performance status over 50
- Life expectancy of at least 3 months
- A stable dose of corticosteroid for at least 7 days to control intracranial pressure and neurological symptoms
- Adequate blood function : absolute neutrophil count > 1.5 x 109/L, platelets count > 100 x 109/L platelets; hemoglobin > 10 g/dl after blood transfusion if required
- Adequate liver function: bilirubin < 1.5 ULN (upper limit of normal), ALT and AST < 2.5 ULN, Prothrombin rate > 75 %
- Adequate renal function: creatinine < 1.2 ULN; proteinuria test 0 or trace (or urine protein concentration < 1g/24h if proteinuria test is + or ++).
- Negative pregnancy test for women of childbearing potential and adequate contraception for men and women.
- systolic arterial blood pressure at rest ≤ 170 mmHg
- Patient must have been informed and must have signed the specific informed consent form.
- holder of a coverage by the health insurance
Who cannot join
- patient belonging to the RPA III or IV
- prior malignant tumor in the recent 5 years or concomitant malignancy
- prior anti-tumoral chemotherapy or radiotherapy
- prior gross resection of the brain tumor
- patient receiving gliadel
- cardiovascular contra-indications to bevacizumab : prior angina pectoris, prior myocardial infarction, prior brain stroke, even transient, distal severe arteriopathy, uncontrolled high blood pressure
Show all 20Show fewer
- anticomitial drug p450 cytochrome inductors
- other substances inducing p450 cytochrome
- proteinuria ≥ 1g/L
- concurrent anticoagulant or platelet anti-aggregant treatment
- congenital haemorrhagic pathology (haemophilia, Willebrandt)
- sign of brain haemorrhage on the RMI initial exam
- non resolved infectious disease
- non controlled arterial hypertension (≥170 mmHg)
- intracranial high pressure not controlled by a stable dose of steroids for at least 7 days
- pregnancy or refusal of the contraception for women and men
- psychiatric, behavioural disorders or geographical situation precluding the administration or follow-up of the protocol (including claustrophobia)
- digestive haemorrhage and / or gastro-duodenal ulcer occurring in the last 3 months
- pregnant, nursing woman, or without contraception
- private individuals of freedom or under tutelage (including legal guardianship)
Trial locations and contacts
1 site in 1 country.
France1 site
Centre Georges François Leclerc
Dijon, Bourgogne-Franche-Comté, 21000
About this study
Official title: Evaluation of the Irinotecan/Bevacizumab Association as Neo-adjuvant and Adjuvant Treatment of Chemoradiation With Temozolomide for Naive Unresectable Glioblastoma. Phase II Randomized Study With Comparison to Chemoradiation With Temozolomide
Treatment of glioblastoma (GBM) is based on surgery when possible, and chemoradiation with temozolomide, which became a standard since the EORTC study (Stupp, 2005). However, the prognosis of unresectable GBM remains poor despite chemoradiation with an estimated 10 month median survival, in the range of the comparable patients in the RPA class V from the EORTC study (Miramanoff, 2006).
Vredenburgh et al. from the Duke University (Durham, NC) reported at ASCO 2006 (fully published in J Clin Oncol, 2007) a 57 % unexpected response rate using a bevacizumab/irinotecan schedule in patients with relapsed GBM or grade 3 astrocytomas. This unusual high response rate, sometimes with major and sustained responses, was confirmed by a cooperative french study of ANOCEF (Guiu et al., 2008). Such a major improvement of treatment effectiveness lead ANOCEF, which federates most of the active neuro-oncology teams in France, to propose a neo-adjuvant and adjuvant bevacizumab-based chemotherapy framing a standard temozolomide-based chemoradiation with the aim to improve the prognosis of unresectable GBM.
Read more
The bevacizumab/temozolomide combination as neo-adjuvant is presently being evaluated by the Duke University. We believe that an ambitious comparison of the bevacizumab/irinotecan-schedule with the ''standard'' temozolomide-based chemoradiation is a fascinating challenge to improve the treatment of this awful disease.
The ANOCEF proposal '' Evaluation of the irinotecan/bevacizumab association as neo-adjuvant and adjuvant treatment of chemoradiation with temozolomide for naive unresectable glioblastoma. Phase II randomized study with comparison to chemoradiation with temozolomide'' has been successfully granted by INCA (Institut National du Fancer, France) through its research program ( PHRC : Programme Hospitalier de Recherche Clinique). Implementation of this program is now starting .
- Conditions
- Naive Unresectable Glioblastoma
- Being tested
- Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures), Temodal/radiotherapy
- Keywords
- unresectable glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures)Drug
Temodal/radiotherapyDrug
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab/Irinoecan | Experimental | Neoadjuvant Treatment Patient will receive bevacizumab 10mg/kg plus irinotecan 125mg/m² 4 times every two weeks.
Radiochemotherapy Then they will receive conformational radiotherapy for 6 weeks (30 Gy, 2Gy/fractions) associated with Temodal ( 75mg/m²/day) from first day up to the end of radiotherapy and 4 injections of Avastin (15mg/kg Day 1, day 15, day 29 and day 43).
Adjuvant treatment:
Patients will receive bevacizumab 15mg/kg plus irinotecan 125mg/m² 12 times every two weeks. Receives: Drug: Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures) |
| Stupp | Active comparator | patient will receive 6 weeks chemotherapy treatment associating conformational 30 Gy (2Gy/ fraction)and Temodal(75mg/m²/day, followed by 6 months adjuvant therapy consisting in 5 days every 28 days of Temodal (150-200mg/m². Receives: Drug: Temodal/radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the rate of non-progressive disease at 6 months after inclusion in each arms
Measured: after half of each arms has been completed at 6 months of treatment
Secondary outcomes (3)
To determine if bevacizumab-based regimen increases the overall survival in comparison of the Stupp regimen
Measured: december 2011
To evaluate if any bevacizumab-based regimen increases the survival without neurologic degradation and the quality of life according to the QLC-C30 and the specific Brain Cancer Module QLQ-BN20 scales.
Measured: december 2011
To evaluate the tolerance of the bevacizumab-based regimens according to the NCI-CTCAE, version 3.0 scale. To record the rate of serious adverse events (mainly the theoretical risk of brain hemorrhage with bevacizumab)
Measured: december 2011
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2009 (estimated)
- Study startJan 2009
- Primary completionJul 2010
- Study completionJan 2011
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 Naive Unresectable 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Georges Francois Leclerc
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France, Association de Neuro-Oncologues d'Expression Francaise, UNICANCER, Hoffmann-La Roche, Pfizer
- Responsible party
- Sponsor
- Investigators
- Bruno Chauffert, Professor, Principal investigator, Centre Hospitalier Universitaire, Amiens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01022918
- Sponsor's protocol ID
- TemAvIr
- Acronym
- TemAvIr
- Status last verified
- Sep 2012
- First submitted
- 26 Nov 2009
- Last updated
- 25 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chauffert B, Feuvret L, Bonnetain F, Taillandier L, Frappaz D, Taillia H, Schott R, Honnorat J, Fabbro M, Tennevet I, Ghiringhelli F, Guillamo JS, Durando X, Castera D, Frenay M, Campello C, Dalban C, Skrzypski J, Chinot O. Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared with temozolomide-chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEFdagger. Ann Oncol. 2014 Jul;25(7):1442-1447. doi: 10.1093/annonc/mdu148. Epub 2014 Apr 9.
PubMed 24723487
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Irinotecan/Bevacizumab Association as Neo-adjuvant and Adjuvant Treatment of Chemoradiation With Temozolomide for Naive Unresectable Glioblastoma. Phase II Randomized Study With Comparison to Chemoradiation With Temozolomide
- ClinicalTrials.gov ID
- NCT01022918
- Acronym / sponsor ID
- TemAvIr / TemAvIr
- Conditions
- Naive Unresectable Glioblastoma
- Keywords
- unresectable glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Centre Georges Francois LeclercUniversity, hospital or other
- Collaborators
- National Cancer Institute, France, Association de Neuro-Oncologues d'Expression Francaise, UNICANCER, Hoffmann-La Roche, Pfizer
- Study start
- Jan 2009
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 1 Dec 2009 (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.
Treatment of glioblastoma (GBM) is based on surgery when possible, and chemoradiation with temozolomide, which became a standard since the EORTC study (Stupp, 2005). However, the prognosis of unresectable GBM remains poor despite chemoradiation with an estimated 10 month median survival, in the range of the comparable patients in the RPA class V from the EORTC study (Miramanoff, 2006).
Vredenburgh et al. from the Duke University (Durham, NC) reported at ASCO 2006 (fully published in J Clin Oncol, 2007) a 57 % unexpected response rate using a bevacizumab/irinotecan schedule in patients with relapsed GBM or grade 3 astrocytomas. This unusual high response rate, sometimes with major and sustained responses, was confirmed by a cooperative french study of ANOCEF (Guiu et al., 2008). Such a major improvement of treatment effectiveness lead ANOCEF, which federates most of the active neuro-oncology teams in France, to propose a neo-adjuvant and adjuvant bevacizumab-based chemotherapy framing a standard temozolomide-based chemoradiation with the aim to improve the prognosis of unresectable GBM.
The bevacizumab/temozolomide combination as neo-adjuvant is presently being evaluated by the Duke University. We believe that an ambitious comparison of the bevacizumab/irinotecan-schedule with the ''standard'' temozolomide-based chemoradiation is a fascinating challenge to improve the treatment of this awful disease.
The ANOCEF proposal '' Evaluation of the irinotecan/bevacizumab association as neo-adjuvant and adjuvant treatment of chemoradiation with temozolomide for naive unresectable glioblastoma. Phase II randomized study with comparison to chemoradiation with temozolomide'' has been successfully granted by INCA (Institut National du Fancer, France) through its research program ( PHRC : Programme Hospitalier de Recherche Clinique). Implementation of this program is now starting .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab/Irinoecan | Experimental | Drug: Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures)Neoadjuvant Treatment Patient will receive bevacizumab 10mg/kg plus irinotecan 125mg/m² 4 times every two weeks. Radiochemotherapy Then they will receive conformational radiotherapy for 6 weeks (30 Gy, 2Gy/fractions) associated with Temodal ( 75mg/m²/day) from first day up to the end of radiotherapy and 4 injections of Avastin (15mg/kg Day 1, day 15, day 29 and day 43). Adjuvant treatment: Patients will receive bevacizumab 15mg/kg plus irinotecan 125mg/m² 12 times every two weeks. |
| Stupp | Active comparator | Drug: Temodal/radiotherapypatient will receive 6 weeks chemotherapy treatment associating conformational 30 Gy (2Gy/ fraction)and Temodal(75mg/m²/day, followed by 6 months adjuvant therapy consisting in 5 days every 28 days of Temodal (150-200mg/m². |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- delay upper or equal to 14 days from stereotaxic biopsy and 28 days from surgical biopsy
- Histopathologically proven diagnosis of glioblastoma (WHO grade IV astrocytoma)
- Patient belonging to the RPA V class or associated
- only supratentorial glioblastoma
- Diagnosis must be obtained by a stereotactic or surgical biopsy
Key exclusion criteria (20 listed)
- patient belonging to the RPA III or IV
- prior malignant tumor in the recent 5 years or concomitant malignancy
- prior anti-tumoral chemotherapy or radiotherapy
- prior gross resection of the brain tumor
- patient receiving gliadel
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 |
|---|---|---|
| Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures) | Drug | Bevacizumab/Irinoecan |
| Temodal/radiotherapy | Drug | Stupp |
Primary outcome
To determine the rate of non-progressive disease at 6 months after inclusion in each arms
Time frame: after half of each arms has been completed at 6 months of treatment
3 secondary outcomes
To determine if bevacizumab-based regimen increases the overall survival in comparison of the Stupp regimen
Time frame: december 2011
To evaluate if any bevacizumab-based regimen increases the survival without neurologic degradation and the quality of life according to the QLC-C30 and the specific Brain Cancer Module QLQ-BN20 scales.
Time frame: december 2011
To evaluate the tolerance of the bevacizumab-based regimens according to the NCI-CTCAE, version 3.0 scale. To record the rate of serious adverse events (mainly the theoretical risk of brain hemorrhage with bevacizumab)
Time frame: december 2011
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 25 Sep 2012.
- Derived from this study: PubMed 24723487Chauffert B, Feuvret L, Bonnetain F, Taillandier L, Frappaz D, Taillia H, Schott R, Honnorat J, Fabbro M, Tennevet I, Ghiringhelli F, Guillamo JS, Durando X, Castera D, Frenay M, Campello C, Dalban C, Skrzypski J, Chinot O. Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared with temozolomide-chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEFdagger. Ann Oncol. 2014 Jul;25(7):1442-1447. doi: 10.1093/annonc/mdu148. Epub 2014 Apr 9.
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.
Bruno Chauffert, Professor principal investigator
Centre Hospitalier Universitaire, Amiens
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 Avastin + Campto / radiotherapy + Temodal + Avastin (4 cures) and Temodal/radiotherapy in people with Naive Unresectable Glioblastoma, run by Centre Georges Francois Leclerc at 1 site in France.
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 19 inclusion and 20 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 25 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 1 site in France. 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?
To determine the rate of non-progressive disease at 6 months after inclusion in each arms (time frame: after half of each arms has been completed at 6 months of treatment). 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 NCT01022918, 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 25 Sep 2012.