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

24. oktober 2018 opdateret af: 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.

Studieoversigt

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

115

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Treatment
erlotinib and bevacizumab
10mg/kg administered intravenously every 2 weeks
Andre navne:
  • Avastin
150 mg/daily orally
Andre navne:
  • Tarceva
  • erlotinib
  • CP-358, 774

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Survival
Tidsramme: 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.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression-free Survival at 12 Months
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Changes in Tumor Blood Flow Based on MR Perfusion
Tidsramme: 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)
Tidsramme: 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.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

7. juli 2009

Primær færdiggørelse (Faktiske)

24. juni 2014

Studieafslutning (Faktiske)

5. juli 2018

Datoer for studieregistrering

Først indsendt

19. juli 2008

Først indsendt, der opfyldte QC-kriterier

19. juli 2008

Først opslået (Skøn)

22. juli 2008

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

26. oktober 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

24. oktober 2018

Sidst verificeret

1. oktober 2018

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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