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

2018년 10월 24일 업데이트: Jeffrey Raizer, Northwestern University

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

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.

연구 개요

상세 설명

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.

연구 유형

중재적

등록 (실제)

115

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

    • California
      • Los Angeles, California, 미국, 90048
        • Cedars-Sinai Medical Center
    • Florida
      • Orlando, Florida, 미국, 32806-2134
        • M.D. Anderson Cancer Center at Orlando
    • Illinois
      • Chicago, Illinois, 미국, 60611-3013
        • Northwestern University, Northwestern Medical Faculty Foundation
      • Evanston, Illinois, 미국, 60201-1781
        • Evanston Hospital
    • South Carolina
      • Charleston, South Carolina, 미국, 29425
        • Hollings Cancer Center at Medical University of South Carolina
    • Texas
      • Dallas, Texas, 미국, 75246
        • Neuro-Oncology Associates at Baylor University Medical Center, Dallas
      • Houston, Texas, 미국, 77030-4009
        • M.D. Anderson Cancer Center at University of Texas
      • Houston, Texas, 미국, 77030
        • The Methodist Hospital Neurological Institute
    • Washington
      • Seattle, Washington, 미국, 19024
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Treatment
erlotinib and bevacizumab
10mg/kg administered intravenously every 2 weeks
다른 이름들:
  • 아바스틴
150 mg/daily orally
다른 이름들:
  • 타세바
  • 엘로티닙
  • CP-358, 774

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Overall Survival
기간: From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months.
Overall survival (OS) will be measured from the start of treatment until death from any cause. At data cut off patients remaining alive will be censored at the last known date of contact.
From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months.

2차 결과 측정

결과 측정
측정값 설명
기간
Progression-free Survival at 12 Months
기간: At 12 months from start of treatment
Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
At 12 months from start of treatment
Response Rate (RR)
기간: From the start of treatment, every 2 cycles (1 cycle = 28 days) during treatment until progressive disease

Response Rate (RR) will be defined as the best response seen during treatment measured by CT/MRI scan every 8 weeks during treatment using McDonald Criteria.

CR=Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients off steroids.

PR=Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable/decreased dose of steroids.

Stable/No Response=Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration. Stable/decreased dose of steroids.

Progressive disease = 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease), worsening of evaluable disease, new lesions/site, failure to return for evaluation due to death or deteriorating condition.

From the start of treatment, every 2 cycles (1 cycle = 28 days) during treatment until progressive disease
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population
기간: From the start of treatment, at the beginning of every cycle (1 cycle = 28 days) during treatment until 30 days after completion of treatment for up to 49 cycles.

Toxicity data for combination treatment of erlotinib and bevacizumab will be collected on day 1 of every cycle (1 cycle = 28 days) during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

From the start of treatment, at the beginning of every cycle (1 cycle = 28 days) during treatment until 30 days after completion of treatment for up to 49 cycles.
Progression Free Survival at 18 Months
기간: At 18 months from start of treatment
Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.
At 18 months from start of treatment

기타 결과 측정

결과 측정
측정값 설명
기간
Changes in Tumor Blood Flow Based on MR Perfusion
기간: Prior to study treatment (after surgery, but before radiation), just before study treatment (within 14 days prior to first treatment) and then every 2 cycles during study treatment, where 1 cycle equals 28 days for a maximum of 49 cycles.
Data from consenting patients will be used to assess of changes in tumor blood flow based on MR perfusion using MRI scans. Two scans will be completed prior to treatment on study; the first after surgery buta before radiation, the second within 14 days before starting combination treatment or erlotinib and bevacizumab. Then scans will be completed every 2 cycles during treatment, where one cycle equals 28 days.
Prior to study treatment (after surgery, but before radiation), just before study treatment (within 14 days prior to first treatment) and then every 2 cycles during study treatment, where 1 cycle equals 28 days for a maximum of 49 cycles.
Gene Methylation Studies (Optional)
기간: At baseline and then plasma only will be collected every odd cycle (1 cycle = 28 days) during treatment for a maximum of 49 cycles.
Tissue and plasma collected from consenting patients in the study will be used to correlate tumor tissue with imaging and outcomes. Tissue will be collected before treatment on study begins and plasma will be collected the first day of treatment (before treatment) and every odd cycle after that, whilst on study treatment. Tissue and plasma analysis will be correlated with patients imaging results and response to to treatment
At baseline and then plasma only will be collected every odd cycle (1 cycle = 28 days) during treatment for a maximum of 49 cycles.

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2009년 7월 7일

기본 완료 (실제)

2014년 6월 24일

연구 완료 (실제)

2018년 7월 5일

연구 등록 날짜

최초 제출

2008년 7월 19일

QC 기준을 충족하는 최초 제출

2008년 7월 19일

처음 게시됨 (추정)

2008년 7월 22일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2018년 10월 26일

QC 기준을 충족하는 마지막 업데이트 제출

2018년 10월 24일

마지막으로 확인됨

2018년 10월 1일

추가 정보

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