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Study Summary
No. BTTC08-01-MDA:.......Brain; CNS......John DeGroot......Neuro Oncology
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Study Summary Title
Study Summary
Number:		BTTC08-01-MDA
Study Title:A Phase II study of Bevacizumab and Erlotinib after Radiation Therapy and Temozolomide in patients with newly diagnosed glioblastoma without MGMT promoter methylation
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Physician New Patient Referral
Name:John DeGrootPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Neuro OncologyReferring MD
Call:		800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2883
Contact us about clinical trials
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General Information
Disease Group:Brain
CNS		Supported By:Brain Tumor Trials Collaborative(BTTC)
Phase of Study:Phase IIReturn
Visit:		Every 2 weeks
Treatment
Agents:		Bevacizumab
Erlotinib
Temozolomide		Home Care:Patients will take temozolomide and erlotinib at home.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:		N/A
Description/
Intervention:		The goal of this clinical research study is to learn if the combination of
bevacizumab and erlotinib after treatment with temozolomide and radiation
therapy will help to control glioblastoma when a certain gene called MGMT is
turned "on". The safety of this drug combination will also be studied.
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Study Objectives / Outcomes
Primary
    • To determine the overall survival for patients with newly diagnosed glioblastoma (GBM) with unmethylated MGMT promoter treated with Bevacizumab and Erlotinib after radiation therapy (RT) + Temozolomide.
      Secondary
        • To determine the 12 and 18 month progression free survival (PFS) for patients with newly diagnosed GBM with unmethylated MGMT promoter treated with Bevacizumab and Erlotinib after RT + Temozolomide.
        • To assess radiographic response rates.
        • To assess changes in tumor blood flow based on MR Perfusion (optional study).
        • To collect tissue and plasma to evaluate for gene methylation studies (Northwestern and Northshore sites only), RT-PCR and correlate with tumor tissue, imaging and outcomes (optional).
        • To collect safety data on the combination of Bevacizumab and Erlotinib for patients with newly diagnosed GBM with unmethylated MGMT promoter treated with Bevacizumab and Erlotinib after RT + Temozolomide.
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        Study Status Information
        Study Activation / Registration Date:
        IRB Review and Approval Date:02/16/2010
        Study Type:Phase Ii Or Phase I/Ii
        Recruitment Status:Closed
        Projected Accrual:115
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        Enrollment Eligibility
        If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.
        Inclusion Criteria:1) Patients with histologically proven newly diagnosed GBM or gliosarcoma will be eligible for consent but will require confirmation of an unmethylated MGMT promoter to be eligible for treatment post RT. If MGMT is indeterminate or methylated, the patient is not eligible. Consent must be obtained prior to starting RT. Determination of MGMT status is strongly recommended to have been determined prior to starting RT to ensure that all treatment options available would still be possible for the ineligible patient. A pathology report of most recent surgery or biopsy must be available at registration.

        2) Patients must have at least 1 block of tumor tissue of sufficient size (at least 1 cm3) for analysis of MGMT status; CUSA (Cavitron ultrasonic aspirator)-derived material is not allowed; fresh frozen tumor tissue acquisition is encouraged for tumor banking at local institution.

        3) Diagnosis must be made by surgical excision, either partial or complete. Stereotactic biopsy will not be allowed because this will not provide sufficient tissue for the MGMT analysis.

        4) The tumor must have a supratentorial component.

        5) Post tumor resection, all patients must have a post operative MRI done no more than 96 hours after surgery or a study > 4 weeks (+/- 7 days) after surgery, but before initiation of radiation treatment in order for an accurate assessment to be done post RT. Another contrast enhanced MRI or CT scan must be performed on no steroids or a stable dose of steroids for 5 days or more, within 14 days before starting treatment with Bevacizumab and Erlotinib.

        6) (5. continued) MR perfusion is optional but recommended. The same type of enhanced scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. Patients who can only get a CT scan will not be able to undergo MR Perfusion: a) Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study. b) The tumor must have no MGMT promoter methylation to qualify for protocol treatment post RT.

        7) No chemotherapy is allowed prior to starting RT + Temozolomide including Gliadel Wafers.

        8) Patients who have started RT + Temozolomide will not be eligible for treatment after RT unless consent was signed before RT began.

        9) (8. continued) Eligible patients will start Bevacizumab and Erlotinib 4 weeks (+/- 7 days) after the completion of RT + Temozolomide. a) RT plans will need to be verified prior to treatment to confirm that the treatment plan was conducted as the protocol outlined or similar based on the PI assessment, such as IMRT. b) The patient must have completed the full course of RT with standard dose temozolomide (75 mg/m2 x 42 days +/- 3 days) prior to initiating Bevacizumab and Erlotinib.

        10) Patients must be > 18 years old.

        11) Patients must have a Karnofsky performance status of >/= 70.

        12) Patients must have adequate bone marrow function (WBC > 3,000/mcL, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function (SGOT/SGPT and bilirubin < 3 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) before starting therapy. These tests must be performed within 7 days prior to registration step 2.

        13) This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate.No exclusion to this study will be based on race.

        14) All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign informed consent prior to registration and before undergoing any study-related procedures. Patients must sign an authorization for the release of their protected health information.
        Exclusion Criteria:1) 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.

        2) Patients must not have proteinuria at screening (within 7 days before registration step 2) as demonstrated by either a) Urine protein:creatinine (UPC) ratio >/= 1.0 at screening OR b) 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).

        3) Patients must not have inadequately controlled hypertension (defined as systolic blood pressure >/=140 and/or diastolic blood pressure >/=90 mmHg)

        4) Patients must not have any prior history of hypertensive crisis or hypertensive encephalopathy

        5) Patients must not have New York Heart Association Grade II or greater congestive heart failure.

        6) Patients must not have history of myocardial infarction or unstable angina within 6 months prior to study enrollment or no evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of </= 2 mm using the analysis of an EKG performed within 14 days before registration step 2.

        7) Patients must not have history of stroke or transient ischemic attack within 6 months prior to study enrollment step 2.

        8) Patients must not have significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease

        9) Patients must not have evidence of bleeding diathesis or coagulopathy. Prothrombin time/international normalized ratio (PT INR) < 1.4 for patients not on warfarin

        10) Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: a) No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) b) In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.

        11) Patients must not have major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment step 2 or the anticipation of need for major surgical procedure during the course of the study, exception is craniotomy.

        12) Patients must not have core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment step 2.

        13) Patients must not have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment step 2.

        14) Patients must not have serious, non-healing wound, ulcer, or bone fracture due to the effects on vasculature by Bevacizumab which may impair healing.

        15) Patients may not be known to be HIV-positive. HIV testing is not required for study participation.

        16) Patients must not have a history of any other cancer (except non-melanoma 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 are ineligible.

        17) Patients must not be pregnant (positive pregnancy test) or breast feeding; pregnancy test must be done within 7 days before registration step 2. Effective contraception (men and women) must be used in subjects of child-bearing potential while on trial and for 3 months after.

        18) Patients may only be on non-enzyme inducing anti-convulsants. If they are on an enzyme inducing anti-convulsant, they may be converted to a non-enzyme inducing anti-convulsants but they will need a 2 week wash out period prior to starting Erlotinib and Bevacizumab.

        19) Patients must be able to comply with study and/or follow-up procedures

        20) Patients may not be on any other experimental agents/clinical trials.

        21) Patients may not have known hypersensitivity to any component of bevacizumab.

        22) Patients with history of recent GI disease or peptic ulcers are excluded from this study unless an exception is approved by study chair.
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        Links
        Registration Number: NCT00720356
        Study Information on Clinical Trials Registry (clinicaltrials.gov)
        Other Links:
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        Results

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