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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 bijgewerkt door: 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.

Studie Overzicht

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

115

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Treatment
erlotinib and bevacizumab
10mg/kg administered intravenously every 2 weeks
Andere namen:
  • Avastin
150 mg/daily orally
Andere namen:
  • Tarceva
  • erlotinib
  • CP-358, 774

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall Survival
Tijdsspanne: 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.

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Progression-free Survival at 12 Months
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Changes in Tumor Blood Flow Based on MR Perfusion
Tijdsspanne: 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)
Tijdsspanne: 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.

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

7 juli 2009

Primaire voltooiing (Werkelijk)

24 juni 2014

Studie voltooiing (Werkelijk)

5 juli 2018

Studieregistratiedata

Eerst ingediend

19 juli 2008

Eerst ingediend dat voldeed aan de QC-criteria

19 juli 2008

Eerst geplaatst (Schatting)

22 juli 2008

Updates van studierecords

Laatste update geplaatst (Werkelijk)

26 oktober 2018

Laatste update ingediend die voldeed aan QC-criteria

24 oktober 2018

Laatst geverifieerd

1 oktober 2018

Meer informatie

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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