Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
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Purpose
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works after radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors |
Drug: bevacizumab Drug: erlotinib hydrochloride |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II Study of Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Without MGMT Promoter Methylation |
- Overall survival [ Time Frame: Every 3 months following the end of treatment due to disease progression ] [ Designated as safety issue: No ]Disease status will be assessed every 3 months by CT or MRI.
- Progression-free survival at 12 and 18 months [ Time Frame: At 12 and 18 months after ending study treatment due to disease progression ] [ Designated as safety issue: No ]Progression free survival will be assessed by CT or MRI
- Radiographic response rates [ Time Frame: Every 8 weeks during treatment ] [ Designated as safety issue: No ]Response will be measured by CT or MRI every 8 weeks during treatment.
- Safety of the combination of erlotinib and bevacizumab in this patient population [ Time Frame: Every 4 weeks during treatment and every 3 months during survival follow up ] [ Designated as safety issue: Yes ]Information on adverse events will be collected before every cycle and during follow up.
| Estimated Enrollment: | 50 |
| Study Start Date: | March 2009 |
| Estimated Study Completion Date: | March 2016 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment
erlotinib and bevacizumab
|
Drug: bevacizumab
10mg/kg administered intravenously every 2 weeks
Other Name: Avastin
Drug: erlotinib hydrochloride
150 mg/daily orally
Other Names:
|
Detailed Description:
OBJECTIVES:
Primary
- To determine the overall survival of patients with newly diagnosed glioblastoma multiforme (GBM) with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide.
Secondary
- To determine the 12- and 24-month progression-free survival (PFS) of patients with newly diagnosed GBM with unmethylated MGMT promoter treated with this regimen.
- To assess radiographic response rates.
- To perform correlative tissue assays.
- To collect safety data on the combination of bevacizumab and erlotinib hydrochloride in patients with newly diagnosed GBM with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide.
OUTLINE: This is a multicenter study.
Patients undergo radiotherapy (either intensity-modulated radiation therapy or 3-D conformal radiotherapy) once daily 5 days a week and receive oral temozolomide concurrently with radiotherapy once daily for 6 weeks (as planned). Patients whose tumor has a methylated MGMT promoter are removed from study.
Approximately 4 weeks after completion of radiotherapy and temozolomide, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment with bevacizumab and erlotinib hydrochloride repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at approximately 30 days and then every 3 months thereafter.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed glioblastoma multiforme (GBM) or gliosarcoma
- Undergoing or plan to undergo treatment with radiotherapy and concurrent temozolomide for 6 weeks
Unmethylated MGMT promoter status must be determined before completing radiotherapy
- Tumor must be MGMT negative to receive bevacizumab and erlotinib hydrochloride
Patients who are post biopsy or tumor resection allowed provided a post-operative MRI is done no more than 96 hours after surgery (in order for an accurate assessment to be done post radiotherapy):
- Evaluable or measurable disease after resection of recurrent tumor is not mandated for eligibility
Patients who started radiotherapy and temozolomide prior to study entry are eligible as long as the gene methylation status is determined before starting bevacizumab and erlotinib hydrochloride
- Radiotherapy plans need to be verified to confirm the treatment plan meets the study requirement based on the PI assessment
- No progressive disease based on MRI or CT scan per the investigators assessment
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- Life expectancy > 12 weeks
- WBC > 3,000/μL
- ANC > 1,500/mm³
- Platelet count > 100,000/mm³
- Hemoglobin > 10 g/dL
- SGOT/SGPT < 3 times upper limit of normal (ULN)
- Bilirubin < 3 times ULN
- Creatinine < 1.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- No significant medical illness 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
No proteinuria at screening, as demonstrated by either of the following:
- Urine protein:creatinine (UPC) ratio < 1.0
- Urine dipstick for proteinuria < 2+ OR ≤ 1g protein by 24-hour urine collection
- No inadequately controlled hypertension (defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg) on antihypertensive medications
- No history of hypertensive crisis or hypertensive encephalopathy
- No New York Heart Association class II-IV congestive heart failure
- No history of myocardial infarction or unstable angina within 6 months prior to study enrollment
- No history of stroke or transient ischemic attack within 6 months of study enrollment
- No symptomatic peripheral vascular disease
- No significant vascular disease (i.e., aortic aneurysm or aortic dissection)
- No evidence of bleeding diathesis or coagulopathy
- No significant traumatic injury within 28 days prior to study enrollment
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- No serious, nonhealing wound, ulcer, or bone fracture
No known HIV positivity
- HIV testing is not required for study participation
- No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years
PRIOR CONCURRENT THERAPY:
- No chemotherapy is allowed prior to starting radiotherapy and temozolomide, including polifeprosan 20 with carmustine implant (Gliadel wafers)
- No major surgical procedure or open biopsy within 28 days prior to study enrollment or the anticipation of need for major surgical procedure during the course of the study
- No core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
Concurrent nonenzyme-inducing anticonvulsants allowed
- More than 2 weeks (before starting erlotinib hydrochloride and bevacizumab) since prior and no concurrent enzyme-inducing anticonvulsant
- No other concurrent experimental agents
- Not concurrently participating in other clinical trials
Contacts and Locations| United States, California | |
| Cedars-Sinai Medical Center | |
| Los Angeles, California, United States, 90048 | |
| United States, Florida | |
| M.D. Anderson Cancer Center at Orlando | |
| Orlando, Florida, United States, 32806-2134 | |
| United States, Illinois | |
| Northwestern University, Northwestern Medical Faculty Foundation | |
| Chicago, Illinois, United States, 60611-3013 | |
| Evanston Hospital | |
| Evanston, Illinois, United States, 60201-1781 | |
| United States, South Carolina | |
| Hollings Cancer Center at Medical University of South Carolina | |
| Charleston, South Carolina, United States, 29425 | |
| United States, Texas | |
| Neuro-Oncology Associates at Baylor University Medical Center, Dallas | |
| Dallas, Texas, United States, 75246 | |
| M.D. Anderson Cancer Center at University of Texas | |
| Houston, Texas, United States, 77030-4009 | |
| The Methodist Hospital Neurological Institute | |
| Houston, Texas, United States, 77030 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 19024 | |
| Principal Investigator: | Jeffrey J. Raizer, MD | Robert H. Lurie Cancer Center |
More Information
No publications provided
| Responsible Party: | Jeffrey Raizer, Principal Investigator, Northwestern University |
| ClinicalTrials.gov Identifier: | NCT00720356 History of Changes |
| Other Study ID Numbers: | NU 07C3, NU 07C3, BTTC08-01, STU00002792 |
| Study First Received: | July 19, 2008 |
| Last Updated: | March 21, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Northwestern University:
|
adult glioblastoma adult gliosarcoma |
Additional relevant MeSH terms:
|
Glioblastoma Nervous System Neoplasms Central Nervous System Neoplasms Gliosarcoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases |
Temozolomide Bevacizumab Erlotinib Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Protein Kinase Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013