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

15 décembre 2015 mis à jour par: 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).

Aperçu de l'étude

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

61

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Barcelona, Espagne, 08035
        • Vall d'Hebron University Hospital
    • New York
      • New York, New York, États-Unis, 10065
        • Memorial Sloan Kettering Cancer Center

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 120 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Homme

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Overall Objective Response
Délai: 2 years
Response will be evaluated in this study using the new international criteria Response Evaluation Criteria in Solid Tumors (RECIST)
2 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

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

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mars 2004

Achèvement primaire (Réel)

1 février 2008

Achèvement de l'étude (Réel)

1 février 2008

Dates d'inscription aux études

Première soumission

10 juin 2004

Première soumission répondant aux critères de contrôle qualité

10 juin 2004

Première publication (Estimation)

11 juin 2004

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

20 janvier 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 décembre 2015

Dernière vérification

1 décembre 2015

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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