Back to resultsStudy of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma (AVF4120s)
Primary Purpose
Glioblastoma, Gliosarcoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Tarceva
Temozolomide
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring Glioblastoma, Gliosarcoma, Bevacizumab, Avastin, Erlotinib, Tarceva, Temozolomide, Temodar
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- University of California San Francisco
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Efficacy Group
Safety Lead-in Group
Arm Description
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
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
Outcomes
Primary Outcome Measures
Overall Survival (OS)
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
Unexpected severe study-related adverse events
Secondary Outcome Measures
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).
Full Information
NCT ID
NCT00525525
First Posted
September 4, 2007
Last Updated
November 5, 2014
Sponsor
University of California, San Francisco
1. Study Identification
Unique Protocol Identification Number
NCT00525525
Brief Title
Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma
Acronym
AVF4120s
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Gliosarcoma
Keywords
Glioblastoma, Gliosarcoma, Bevacizumab, Avastin, Erlotinib, Tarceva, Temozolomide, Temodar
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
74 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Efficacy Group
Arm Type
Experimental
Arm Description
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
Arm Title
Safety Lead-in Group
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Patients are given 10 mg/kg IV Q2 weeks.
Intervention Type
Drug
Intervention Name(s)
Tarceva
Other Intervention Name(s)
Erlotonib
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Overall survival was defined from the date of diagnosis to date of death from any cause
Time Frame
Approximately 6-24 months
Title
Unexpected Toxicities During First 2 Cycles of Study Drug
Description
Unexpected severe study-related adverse events
Time Frame
Within 8 weeks of initiating study therapy
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
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).
Time Frame
Approximately 6 months to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael D. Prados, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24637230
Citation
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.
Results Reference
result
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Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma
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