GlioblastomaPhase 2AVF4120sNCT00525525
Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma
A Phase 2 study testing Bevacizumab, Tarceva and Temozolomide in people with Glioblastoma and Gliosarcoma, run by University of California, San Francisco at 1 site in United States.
Trial summary
This is a phase II study of Bevacizumab plus Temodar and Tarceva in patients with non-progressive glioblastoma or gliosarcoma. Patients must have stable disease immediately following a standard course of up-front radiotherapy and Temodar. All patients will receive Bevacizumab, Temodar and Tarceva. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma
- What is being tested?
- Bevacizumab, Tarceva and Temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically proven, non-progressive glioblastoma multiforme (GBM) or gliosarcoma (GS) with stable disease immediately following XRT + TMZ. All patients will receive Bevacizumab plus Tarceva and TMZ.
- Biopsy or resection must have been performed prior to RT + TMZ.
- No chemotherapy is allowed prior to starting RT + TMZ, including Gliadel Wafers.
- Patients will have started RT + TMZ prior to registration and study entry and are eligible as long as they do not have progressive disease and can start Bevacizumab + TMZ and Tarceva within 4 weeks after the completion of RT + TMZ. Patients MUST have been treated with at least 54 Gy radiotherapy (60 Gy recommended) and MUST have received Temodar concurrently with radiotherapy for eligibility for this study.
- Patients may or may not have measurable or evaluable disease on contrast MR imaging. A post-radiotherapy MRI scan must document stable disease.
- Patients must be > 18 years old and with a life expectancy > 12 weeks.
- Patients must have a Karnofsky performance status of ≥ 70.
- Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) before starting therapy. These tests must be performed within 14 days prior to initial treatment.
Who cannot join
- Patients must not have evidence of recent hemorrhage on baseline MRI of the brain, with the following exceptions: presence of hemosiderin, resolving hemorrhage changes related to surgery, presence of punctuate hemorrhage in the tumor.
- Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate this therapy or any disease that will obscure toxicity or dangerously alter drug metabolism.
- Patients must not have proteinuria at screening as demonstrated by either
- Urine protein: creatinine (UPC) ratio ³ 1.0 at screening OR
- Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- Patients must not have inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg) on antihypertensive medications.
Show all 9Show fewer
- Patients must not have any prior history of hypertensive crisis or hypertensive encephalopathy.
- Patients must not have New York Heart Association Grade II or greater congestive heart failure (see Appendix E).
- Patients must not have history of myocardial infarction or unstable angina within 12 months prior to study enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase II Study of Bevacizumab Plus Temodar and Tarceva After Radiation Therapy and Temodar in Patients With Newly Diagnosed Glioblastoma or Gliosarcoma Who Are Stable Following Radiation
This is a phase II study of Bevacizumab plus Temodar and Tarceva in patients with non-progressive glioblastoma or gliosarcoma. Patients must have stable disease immediately following a standard course of up-front radiotherapy and Temodar. All patients will receive Bevacizumab, Temodar and Tarceva. A total of 60 patients will be enrolled. Our hypothesis is that the combination of Bevacizumab plus Temodar and Tarceva will increase survival over that seen in historical controls who have newly diagnosed, non-progressive glioblastoma or gliosarcoma following radiotherapy plus Temodar and use Temodar alone.
Read the detailed description
Patients with newly diagnosed glioblastoma or gliosarcoma are treated with standard of care radiation and temozolomide, plus the addition of Bevacizumab and Tarceva. The dose of temozolomide, Bevacizumab and radiation are the same for all patients. Tarceva dose is based upon the use of enzyme inducing anti-epileptic agents. Tarceva is given daily; Bevacizumab is given every 2 weeks; radiation is for 6 weeks, and temozolomide is given daily during radiotherapy and then in the adjuvant setting, is given on a 5-day schedule every 28 days. Patients are followed for progression and survival. The measure of response is MR scanning every 2 months. Dose adjustments are based upon the specific toxicity of the agent in question which differs for each agent (Bevacizumab, temozolomide, or Tarceva). Patients are not randomized, but assigned to an arm based on use of anti-epileptic agents.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Bevacizumab, Tarceva, Temozolomide
- Keywords
- Glioblastoma, Gliosarcoma, Bevacizumab, Avastin, Erlotinib, Tarceva, Temozolomide, Temodar
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Patients are given 10 mg/kg IV Q2 weeks.
TarcevaDrug
Also called Erlotonib
Patients receive 150 mg PO daily. If patients are not experiencing intolerable toxicity, they may escalate their dose to 200 mg PO daily. If patients are experiencing intolerable toxicity, their dose will be held until the toxicity improves or resolves, then re-treated at a lower dose level, i.e. 100 mg PO daily.
TemozolomideDrug
Patients receive 200 mg/m2 for Days 1-5 of every 28 day cycle. Although the calendar days may be slightly altered, the patient should always receive this dose for 5 days within a treatment cycle. If the patient experiences certain toxicities specified in the protocol, Temodar will be held then given at a reduced dose, i.e. 150 mg/m2 Days 1-5.
| Study group | Role | What they receive |
|---|---|---|
| Efficacy Group | Experimental | Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity Receives: Drug: Bevacizumab; Drug: Tarceva; Drug: Temozolomide |
| Safety Lead-in Group | Other | Fractionated radiotherapy in daily doses of 1.8-2.0 Gy delivered 5 days per week over ~6 weeks, to a total dose of 59.4 to 60 Gy.
Adjuvant temozolomide 200 mg/m^2/d x 5 d per 28-d cycle; Erlotinib 150-200 mg/d (or 500-600 mg/d for patients on enzyme-inducing antiepileptic drugs) on a continuous basis 7 days per week; Bevacizumab 10 mg/kg every 2 weeks Receives: Drug: Bevacizumab; Drug: Tarceva; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall survival was defined from the date of diagnosis to date of death from any cause
Measured: Approximately 6-24 months
Unexpected Toxicities During First 2 Cycles of Study Drug
Unexpected severe study-related adverse events
Measured: Within 8 weeks of initiating study therapy
Secondary outcomes (1)
Progression-free Survival
Progression-free survival was defined from the date of diagnosis to the date that progressive disease was first observed on imaging, or the date at which nonreversible neurologic progression or permanently increased corticosteroid requirement, death from any cause, or early discontinuation of treatment. Imaging guidelines were used to evaluate progression: (i) 25% increase in the sum of products of all measurable lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline; (ii) clear worsening of any assessable disease; (iii) appearance of any new lesion/site; and (iv) clear clinical worsening or failure to return for evaluation as a result of death or deteriorating condition (unless clearly unrelated to this cancer).
Measured: Approximately 6 months to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Prados, University of California, San Francisco
- Investigators
- Michael D. Prados, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00525525
- Sponsor's protocol ID
- 07105
- Acronym
- AVF4120s
- Status last verified
- Nov 2014
- First submitted
- 4 Sep 2007
- Last updated
- 14 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Clarke JL, Molinaro AM, Phillips JJ, Butowski NA, Chang SM, Perry A, Costello JF, DeSilva AA, Rabbitt JE, Prados MD. A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. Neuro Oncol. 2014 Jul;16(7):984-90. doi: 10.1093/neuonc/nou029.
PubMed 24637230
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Bevacizumab Plus Temodar and Tarceva After Radiation Therapy and Temodar in Patients With Newly Diagnosed Glioblastoma or Gliosarcoma Who Are Stable Following Radiation
- ClinicalTrials.gov ID
- NCT00525525
- Acronym / sponsor ID
- AVF4120s / 07105
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Glioblastoma, Gliosarcoma, Bevacizumab, Avastin, Erlotinib, Tarceva, Temozolomide, Temodar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 5 Sep 2007 (estimated)
- Results
- Posted 14 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II study of Bevacizumab plus Temodar and Tarceva in patients with non-progressive glioblastoma or gliosarcoma. Patients must have stable disease immediately following a standard course of up-front radiotherapy and Temodar. All patients will receive Bevacizumab, Temodar and Tarceva. A total of 60 patients will be enrolled. Our hypothesis is that the combination of Bevacizumab plus Temodar and Tarceva will increase survival over that seen in historical controls who have newly diagnosed, non-progressive glioblastoma or gliosarcoma following radiotherapy plus Temodar and use Temodar alone.
Detailed description
Patients with newly diagnosed glioblastoma or gliosarcoma are treated with standard of care radiation and temozolomide, plus the addition of Bevacizumab and Tarceva. The dose of temozolomide, Bevacizumab and radiation are the same for all patients. Tarceva dose is based upon the use of enzyme inducing anti-epileptic agents. Tarceva is given daily; Bevacizumab is given every 2 weeks; radiation is for 6 weeks, and temozolomide is given daily during radiotherapy and then in the adjuvant setting, is given on a 5-day schedule every 28 days. Patients are followed for progression and survival. The measure of response is MR scanning every 2 months. Dose adjustments are based upon the specific toxicity of the agent in question which differs for each agent (Bevacizumab, temozolomide, or Tarceva). Patients are not randomized, but assigned to an arm based on use of anti-epileptic agents.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Efficacy Group | Experimental | Drug: Bevacizumab, Drug: Tarceva, Drug: TemozolomidePatients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity |
| Safety Lead-in Group | Other | Drug: Bevacizumab, Drug: Tarceva, Drug: TemozolomideFractionated radiotherapy in daily doses of 1.8-2.0 Gy delivered 5 days per week over ~6 weeks, to a total dose of 59.4 to 60 Gy. Adjuvant temozolomide 200 mg/m^2/d x 5 d per 28-d cycle; Erlotinib 150-200 mg/d (or 500-600 mg/d for patients on enzyme-inducing antiepileptic drugs) on a continuous basis 7 days per week; Bevacizumab 10 mg/kg every 2 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with histologically proven, non-progressive glioblastoma multiforme (GBM) or gliosarcoma (GS) with stable disease immediately following XRT + TMZ. All patients will receive Bevacizumab plus Tarceva and TMZ.
- Biopsy or resection must have been performed prior to RT + TMZ.
- No chemotherapy is allowed prior to starting RT + TMZ, including Gliadel Wafers.
- Patients will have started RT + TMZ prior to registration and study entry and are eligible as long as they do not have progressive disease and can start Bevacizumab + TMZ and Tarceva within 4 weeks after the completion of RT + TMZ. Patients MUST have been treated with at least 54 Gy radiotherapy (60 Gy recommended) and MUST have received Temodar concurrently with radiotherapy for eligibility for this study.
- Patients may or may not have measurable or evaluable disease on contrast MR imaging. A post-radiotherapy MRI scan must document stable disease.
Key exclusion criteria (9 listed)
- Patients must not have evidence of recent hemorrhage on baseline MRI of the brain, with the following exceptions: presence of hemosiderin, resolving hemorrhage changes related to surgery, presence of punctuate hemorrhage in the tumor.
- Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate this therapy or any disease that will obscure toxicity or dangerously alter drug metabolism.
- Patients must not have proteinuria at screening as demonstrated by either
- Patients must not have inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg) on antihypertensive medications.
- Patients must not have any prior history of hypertensive crisis or hypertensive encephalopathy.
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 |
|---|---|---|
| BevacizumabPatients are given 10 mg/kg IV Q2 weeks. | Drug | Efficacy Group, Safety Lead-in Group |
| TarcevaAlso: ErlotonibPatients receive 150 mg PO daily. If patients are not experiencing intolerable toxicity, they may escalate their dose to 200 mg PO daily. If patients are experiencing intolerable toxicity, their dose will be held until the toxicity improves or resolves, then re-treated at a lower dose level, i.e. 100 mg PO daily. | Drug | Efficacy Group, Safety Lead-in Group |
| TemozolomidePatients receive 200 mg/m2 for Days 1-5 of every 28 day cycle. Although the calendar days may be slightly altered, the patient should always receive this dose for 5 days within a treatment cycle. If the patient experiences certain toxicities specified in the protocol, Temodar will be held then given at a reduced dose, i.e. 150 mg/m2 Days 1-5. | Drug | Efficacy Group, Safety Lead-in Group |
Primary outcome
Overall Survival (OS)
Time frame: Approximately 6-24 months
Overall survival was defined from the date of diagnosis to date of death from any cause
Unexpected Toxicities During First 2 Cycles of Study Drug
Time frame: Within 8 weeks of initiating study therapy
Unexpected severe study-related adverse events
1 secondary outcome
Progression-free Survival
Time frame: Approximately 6 months to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24637230Clarke JL, Molinaro AM, Phillips JJ, Butowski NA, Chang SM, Perry A, Costello JF, DeSilva AA, Rabbitt JE, Prados MD. A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. Neuro Oncol. 2014 Jul;16(7):984-90. doi: 10.1093/neuonc/nou029.
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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.
Michael D. Prados, MD principal investigator
University of California, San Francisco
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 Bevacizumab, Tarceva and Temozolomide in people with Glioblastoma and Gliosarcoma, run by University of California, San Francisco at 1 site in United States.
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 8 inclusion and 9 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 14 Nov 2014. 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 United States. 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?
Yes. Results are posted in the registry (first posted 14 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Survival (OS) (time frame: Approximately 6-24 months). 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 NCT00525525, 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 14 Nov 2014; AzTrials last refreshed its copy on 7 Nov 2026.