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A Phase II Study of Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Without MGMT Promoter Methylation


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Brain and Central Nervous System Tumors

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Trial Information

A Phase II Study of Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Without MGMT Promoter Methylation


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

Disease status will be assessed every 3 months by CT or MRI.

Outcome Time Frame:

Every 3 months following the end of treatment due to disease progression

Safety Issue:

No

Principal Investigator

Jeffrey J. Raizer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Robert H. Lurie Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NU 07C3

NCT ID:

NCT00720356

Start Date:

March 2009

Completion Date:

March 2016

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult glioblastoma
  • adult gliosarcoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Gliosarcoma

Name

Location

Cedars-Sinai Medical CenterLos Angeles, California  90048
M.D. Anderson Cancer Center at University of TexasHouston, Texas  77030
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
Evanston HospitalEvanston, Illinois  60201-1781
Northwestern University, Northwestern Medical Faculty FoundationChicago, Illinois  60611-3013
The Methodist Hospital Neurological InstituteHouston, Texas  77030
Neuro-Oncology Associates at Baylor University Medical Center, DallasDallas, Texas  75246