Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Jeffrey Raizer, Northwestern University
ClinicalTrials.gov Identifier:
NCT00720356
First received: July 19, 2008
Last updated: March 31, 2014
Last verified: March 2014
  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

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 2017
Estimated Primary Completion Date: March 2016 (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:
  • erlotinib
  • CP-358, 774
  • Tarceva

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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720356

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
Sponsors and Collaborators
Northwestern University
M.D. Anderson Cancer Center
Investigators
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 31, 2014
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
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
Bevacizumab
Temozolomide
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on October 16, 2014