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Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme

21. juli 2016 oppdatert av: SCRI Development Innovations, LLC

A Phase II Trial of Concurrent Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib in the First-Line Treatment of Patients With Glioblastoma Multiforme

The mechanism of action of sorafenib makes it an interesting drug to investigate in the treatment of patients with glioblastoma multiforme. Efficacy of agents with anti-angiogenic activity has already been demonstrated and the PDGF receptor target may also be pertinent in glioblastoma. The combination of temozolomide plus sorafenib has been investigated previously in the treatment of patients with advanced melanoma. The combination was generally well tolerated; in previously untreated patients, a standard dose of sorafenib (400mg PO bid) was administered with temozolomide 150mg/m2 PO daily for 5 days, repeated every 28 days (23).

In this multicenter phase II study, patients with newly diagnosed glioblastoma will receive standard treatment, including initial debulking surgical resection (if feasible) followed by high-dose radiation therapy with concurrent temozolomide. After completion of radiation therapy, patients will continue treatment with temozolomide (150mg/m2 days 1-5) and sorafenib (400mg PO bid daily), repeated at 28-day intervals for 6 cycles.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.

Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.

After completion of combined modality therapy, patients will have 4 weeks without any therapy.

Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be administered on days 1-28, repeated for 6 courses concurrently with temozolomide

Studietype

Intervensjonell

Registrering (Faktiske)

47

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Florida
      • Fort Myers, Florida, Forente stater, 33901
        • Florida Cancer Specialists
    • Georgia
      • Gainesville, Georgia, Forente stater, 30501
        • Northeast Georgia Medical Center
    • Maryland
      • Bethesda, Maryland, Forente stater, 20817
        • Center for Cancer and Blood Disorders
    • Michigan
      • Grand Rapids, Michigan, Forente stater, 49503
        • Grand Rapids Clinical Oncology Program
    • Nebraska
      • Omaha, Nebraska, Forente stater, 68114
        • Methodist Cancer Center
    • Ohio
      • Cincinnati, Ohio, Forente stater, 45242
        • Oncology Hematology Care
    • South Carolina
      • Spartanburg, South Carolina, Forente stater, 29303
        • Spartanburg Regional Medical Center
    • Tennessee
      • Nashville, Tennessee, Forente stater, 37203
        • Tennessee Oncology
    • Texas
      • San Antonio, Texas, Forente stater, 78258
        • South Texas Oncology And Hematology
    • Virginia
      • Richmond, Virginia, Forente stater, 23235
        • Virginia Cancer Institute

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
  2. Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
  3. No previous treatment for glioblastoma except for previous surgical debulking (i.e. no previous radiotherapy, local chemotherapy, or systemic therapy).
  4. ECOG performance status 0 or 1 (See Appendix C)
  5. Age ≥ 18 years
  6. Adequate bone marrow function: hemoglobin ≥ 9.0g/dL; ANC ≥ 1500/μL; platelet count ≥ 100,000/μL.

  7. Adequate liver function

    • Total bilirubin ≤ 1.5 x ULN
    • ALT and AST ≤ 2.5 x ULN
  8. Serum creatinine < 1.5 x ULN
  9. Women of child-bearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women must agree to not breast feed while receiving study treatment.
  10. Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) while receiving study treatment. Women should use adequate birth control for at least 3 months after the last administration of sorafenib.
  11. INR < 1.5 or PT/PTT within normal limits in patients not receiving anticoagulation. However, patients receiving anticoagulation treatment with an agent such as warfarin or heparin are also eligible. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
  12. Patients must have the ability to understand and the willingness to sign written informed consent. A signed informed consent must be obtained prior to any study-specific procedures.

Exclusion Criteria:

  1. Patients must have the ability to swallow whole pills.
  2. Active cardiac disease: congestive heart failure > class 2 NYHA (Appendix D); unstable angina or new onset angina within the last 3 months; myocardial infarction within the last 6 months.
  3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  4. Uncontrolled hypertension defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optimal medical management
  5. Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection
  6. Active clinically serious infection > grade 2
  7. Thrombotic or embolic events including cerebral vascular accident or TIAs within the past 6 months
  8. Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of the first dose of sorafenib
  9. Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of the first dose of sorafenib
  10. Serious non-healing wound, ulcer, or bone fracture
  11. Evidence or history of bleeding diathesis or coagulopathy
  12. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of beginning treatment with sorafenib
  13. Use of St. John's Wort or rifampicin
  14. Known or suspected allergy to sorafenib or temozolomide
  15. Any malabsorption problem
  16. Other active malignancies, or treatment for invasive cancer within the last 2 years

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Combination Therapy

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months
Stråling: Radiation Therapy
2 Gy/fraction, single daily fractions M-F, to 60 Gy total
Legemiddel: Temozolomide

In Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily

In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles

Andre navn:
  • Temodar
Legemiddel: Sorafenib
In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months
Andre navn:
  • Nexavar

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-free Survival
Tidsramme: 18 months
Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
18 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Overall Survival
Tidsramme: 18 months
Defined as Day 1 of protocol treatment to date of death from any cause.
18 months
Objective Response
Tidsramme: every 8 weeks until disease progression, estimated 18 months

The number of patients with complete or partial responses measured from the time of initial response to documented tumor progression. Radiologic response was defined using the Macdonald criteria.

The Macdonald criteria divides response into 4 types of response based on imaging (MRI) and clinical features, as follows: 1) complete response (CR); 2) partial response (PR); 3) stable disease (SD); and 4) progression (PD).

Criteria:

CR: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions. No corticosteroids, clinically stable or improved.

PR: >=50% decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no new lesions. Stable or reduced corticosteroids, clinically stable or improved.

SD: does not qualify for complete response, partial response or progression. Clinically stable.

PD: >= 25% increase in enhancing lesions, any new lesions. Clinical deterioration.
every 8 weeks until disease progression, estimated 18 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

SCRI Development Innovations, LLC

Samarbeidspartnere

Bayer

Etterforskere

  • Studiestol: John D. Hainsworth, M.D., SCRI Development Innovations, LLC

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. april 2007

Primær fullføring (Faktiske)

1. juni 2008

Studiet fullført (Faktiske)

1. august 2010

Datoer for studieregistrering

Først innsendt

15. oktober 2007

Først innsendt som oppfylte QC-kriteriene

15. oktober 2007

Først lagt ut (Anslag)

16. oktober 2007

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

1. september 2016

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. juli 2016

Sist bekreftet

1. juli 2016

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • SCRI CNS 09

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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