- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00085566
Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer
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).
Studienübersicht
Status
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienorte
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Barcelona, Spanien, 08035
- Vall d'Hebron University Hospital
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New York
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New York, New York, Vereinigte Staaten, 10065
- Memorial Sloan Kettering Cancer Center
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: 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. |
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Overall Objective Response
Zeitfenster: 2 years
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Response will be evaluated in this study using the new international criteria Response Evaluation Criteria in Solid Tumors (RECIST)
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2 years
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Mitarbeiter und Ermittler
Mitarbeiter
Ermittler
- Hauptermittler: Lauren E. Abrey, MD, Memorial Sloan Kettering Cancer Center
- Hauptermittler: Howard I. Scher, MD, Memorial Sloan Kettering Cancer Center
- Hauptermittler: Neal Rosen, MD, Memorial Sloan Kettering Cancer Center
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Nervensystems
- Neubildungen nach histologischem Typ
- Neubildungen
- Urogenitale Neoplasmen
- Neubildungen nach Standort
- Neubildungen, Drüsen und Epithelien
- Genitale Neubildungen, männlich
- Prostataerkrankungen
- Astrozytom
- Gliom
- Neubildungen, Neuroepithel
- Neuroektodermale Tumoren
- Neoplasmen, Keimzelle und Embryonal
- Neubildungen, Nervengewebe
- Prostataneoplasmen
- Glioblastom
- Neubildungen des Nervensystems
- Neubildungen des zentralen Nervensystems
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Enzym-Inhibitoren
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Proteinkinase-Inhibitoren
- Gefitinib
- Everolimus
Andere Studien-ID-Nummern
- 04-010
- MSKCC-04010
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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