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Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer

15. december 2015 opdateret af: Memorial Sloan Kettering Cancer Center

A Phase I/II Trial to Assess the Tolerability of RAD 001 With Gefitinib in Patients With Glioblastoma Multiforme and Prostate Cancer and Efficacy in Patients With Castrate Metastatic Prostate Cancer

RATIONALE: Everolimus may stop the growth of tumor cells by stopping blood flow to the tumor. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining everolimus with gefitinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with gefitinib and to see how well they work in treating patients with progressive glioblastoma multiforme or (progressive metastatic prostate cancer closed to accrual 10/19/06).

Studieoversigt

Detaljeret beskrivelse

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of everolimus when given in combination with gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer -closed to accrual as of 10/19/2006). (Phase I)
  • Determine the safety and efficacy of this regimen in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to accrual as of 10/19/2006). (Phase II)

Secondary

  • Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib in patients treated with this regimen.
  • Determine the association between clinical outcomes and markers that may predict sensitivity of a tumor in patients treated with this regimen.
  • Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens and peripheral blood mononuclear cells from these patients.

OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus followed by a phase II study.

  • Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

61

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

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

Studiesteder

    • New York
      • New York, New York, Forenede Stater, 10065
        • Memorial Sloan Kettering Cancer Center
      • Barcelona, Spanien, 08035
        • Vall d'Hebron University Hospital

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 til 120 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Han

Beskrivelse

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Glioblastoma multiforme (GBM) (phase I only)

      • Progressive disease despite standard therapy
      • Progressive disease based on 1 of the following:

        • New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
        • New or prior lesions that have increased in size by physical examination
      • Patients who had prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true disease progression (rather than radiation necrosis) by positron-emission tomography scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation
    • Castrate metastatic prostate cancer (closed to accrual as of 10/19/2006) (phase I and II)

      • Progressive disease despite standard therapy AND castrate levels < 50 ng/dL of testosterone
      • Progressive disease based on 1 or more of the following:

        • A minimum of 3 rising levels of prostate-specific antigen (PSA) that are obtained 1 or more weeks apart OR 2 rising PSA values obtained more than 1 month apart with at least a 25% increase over the range of values
        • New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
        • New metastatic lesions
      • Patients on an antiandrogen as part of initial therapy must show disease progression after discontinuation of the antiandrogen
      • Patients who have not undergone surgical orchiectomy must continue with medical therapy (e.g., gonadotropin-releasing hormone analogs) to maintain castrate levels of serum testosterone
  • No brain metastases

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • More than 3 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3

Hepatic

  • ALT and AST ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 mg/dL

Renal

  • Creatinine within 1.5 times ULN (< 1.95 mg/dL at MSKCC)

Cardiovascular

  • No significant cardiovascular disease
  • No congestive heart failure
  • No New York Heart Association class III or IV cardiac disease
  • No active angina pectoris
  • No myocardial infarction within the past 6 months

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious medical illness
  • No severe infection
  • No severe malnutrition
  • No other active malignancy except non-melanoma skin cancer

    • Patients are not considered to have an active malignancy if they have completed prior therapy and currently have a < 30% risk for relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent biological therapy
  • No concurrent immunotherapy

Chemotherapy

  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics

Radiotherapy

  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics
  • Prior recent resection of recurrent or progressive GBM allowed provided patient has recovered
  • More than 4 weeks since prior major surgery

Other

  • Recovered from all prior therapy
  • More than 4 weeks since prior investigational anticancer drugs
  • No concurrent anticonvulsant that interacts with CYP3A4 (e.g., phenytoin, carbamazepine, or phenobarbital)
  • No other concurrent cytotoxic therapy
  • No other concurrent investigational or commercial agents or therapies for the malignancy

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: Everolimus (RAD-001) and Gefitinib

•Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

•Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Overall Objective Response
Tidsramme: 2 years
Response will be evaluated in this study using the new international criteria Response Evaluation Criteria in Solid Tumors (RECIST)
2 years

Samarbejdspartnere og efterforskere

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

Samarbejdspartnere

Efterforskere

  • Ledende efterforsker: Lauren E. Abrey, MD, Memorial Sloan Kettering Cancer Center
  • Ledende efterforsker: Howard I. Scher, MD, Memorial Sloan Kettering Cancer Center
  • Ledende efterforsker: Neal Rosen, MD, Memorial Sloan Kettering Cancer Center

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

1. marts 2004

Primær færdiggørelse (Faktiske)

1. februar 2008

Studieafslutning (Faktiske)

1. februar 2008

Datoer for studieregistrering

Først indsendt

10. juni 2004

Først indsendt, der opfyldte QC-kriterier

10. juni 2004

Først opslået (Skøn)

11. juni 2004

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

20. januar 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. december 2015

Sidst verificeret

1. december 2015

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 .

Kliniske forsøg med everolimus

Abonner