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Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

3 novembre 2016 mis à jour par: Suresh S. Ramalingam, Emory University
This is a Phase 1b pre-operative lung cancer trial wherein patients with operable lung cancer will be treated with RAD001 to evaluate the target effects of this compounds on relevant molecular pathways and on the 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) uptake of the tumor by a positron emission tomography (PET) scan at baseline and immediately prior to surgery. The safety profile of RAD001 will also be evaluated.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

This is a Phase 1b pre-operative lung cancer trial wherein patients with operable lung cancer will be treated with RAD001 for 3-4 weeks to study the effects of the novel agent in relevant molecular pathways. The study will also assess the FDG uptake of the tumor at baseline and upon completion of therapy (before surgery) with a PET scan. The safety profile of RAD001 will also be evaluated.

New agents and regimens are urgently needed for lung cancer treatment. With the development of novel agents and small molecules designed to curtail the aggressive aspects of this disease, some progress has been realized. However, much more effort and insight will be required for further real gains to be made. We propose that studying the mammalian target of rapamycin (mTOR) axis, known to be abnormal in non-small cell lung cancer (NSCLC), and translating that knowledge into therapeutic adjustments can lead to meaningful advances in lung cancer treatment.

Approximately 35 patients will participate at Winship Cancer Institute of Emory University in Atlanta, Georgia.

Type d'étude

Interventionnel

Inscription (Réel)

33

Phase

  • 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

  • États-Unis
    • Georgia
      • Atlanta, Georgia, États-Unis, 30322
        • Emory University Winship Cancer Institute

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 et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Patient must have histologically confirmed Stage I-IIIA non-small cell lung cancer (NSCLC) which is accessible to biopsy.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
  • Life-expectancy greater than 6 months.
  • Adequate bone marrow, renal, hepatic, pulmonary and cardiac function as defined in the protocol.
  • Patient must be at least 18 years of age.
  • Must meet pre-entry requirements for timing of study parameters as specified in section 7.0.
  • Female patients of child-bearing potential must have a negative serum pregnancy test within 48 hours of study initiation and be non-lactating.
  • Patients of child-bearing potential must agree to use an effective form of contraception while on study and for 3 months following completion of study treatment.
  • The use of granulocyte-colony stimulating factor (G-CSF) will be permitted in study participants.
  • Final eligibility for a clinical trial is determined by the health professionals conducting the trial.

Exclusion Criteria:

  • Patient has received previous treatment for NSCLC.
  • Known hypersensitivity to everolimus, sirolimus, or any of its excipients.
  • Patient is pregnant or breast-feeding.
  • Patient has incurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patient is unable to swallow RAD001 tablet.
  • History of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of the malignancy being present within the past five years.
  • History of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80. Symptoms may include any reaction such as bronchospasm, generalized urticaria, systolic BP ≤ 80mm Hg, and angioedema.
  • Final eligibility for a clinical trial is determined by the health professionals conducting the trial.

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: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: 1
RAD001 5 mg/day for 21 days sequentially.
Médicament: RAD001
Patients will be assigned to one of three treatment arms with RAD001 doses of 5, and 10 mg/day for 21-28 days sequentially taken orally in tablet form.
Autres noms:
  • Évérolimus
Comparateur actif: 3
RAD001 10 mg/day for 21 days sequentially.
Médicament: RAD001
Patients will be assigned to one of three treatment arms with RAD001 doses of 5, and 10 mg/day for 21-28 days sequentially taken orally in tablet form.
Autres noms:
  • Évérolimus
Aucune intervention: Control
Patients who are eligible for the study but choose not to receive RAD001 treatment.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Clinical Response as Assessed Metabolically by Changes in Positron Emission Tomography (PET) Scan Between Baseline and Immediately Prior to Surgery.
Délai: Day 21
All patients had baseline imaging in a fasted state with 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18FDG)-PET scan and a repeat scan at 3 to 4 weeks later using routine clinical protocol for patient preparation, radiotracer administration and data acquisition. The repeat imaging occurred no longer than 24 hours before surgical resection.
Day 21
Effects of RAD001 on the Regulation of Key Proteins Involved With the Mammalian Target of Rapamycin (mTOR) Axis in Tumor Specimens and Buccal Mucosa in Patients With Operable Non-small Cell Lung Cancer (NSCLC).
Délai: 6 months
Changes in the expression of key signaling proteins in the mTOR/phosphatidylinositol 3-kinase (PI3K) pathway were determined by immunohistochemistry using previously published protocols and manufacturers' recommendations for antigen retrieval and antibody dilution along with positive and negative controls. Two investigators assessed protein expression jointly by light microscopy. The degree of expression was assessed by intensity (0, 1+, 2+, 3+) and percentage of cell staining in line with published algorithm. A derivative score (immunoscore) ranging between 0 and 300 was calculated as the product of intensity and percent cell staining.
6 months
Inhibition of Proliferation (Ki67) and Induction of Apoptosis (TUNEL Assay) in Tumor Specimens and Buccal Mucosa.
Délai: 6 months
6 months

Mesures de résultats secondaires

Mesure des résultats
Délai
Safety and Tolerability of RAD001 as Pre-operative Therapy.
Délai: 6 months
6 months
Duration of Hospital Stay Following Surgery.
Délai: 6 months
6 months

Collaborateurs et enquêteurs

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

Parrainer

Emory University

Les enquêteurs

  • Chercheur principal: Suresh Ramalingam, MD, Emory University Winship Cancer Institute

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 novembre 2006

Achèvement primaire (Réel)

1 décembre 2013

Achèvement de l'étude (Réel)

1 décembre 2013

Dates d'inscription aux études

Première soumission

17 novembre 2006

Première soumission répondant aux critères de contrôle qualité

17 novembre 2006

Première publication (Estimation)

22 novembre 2006

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

21 décembre 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

3 novembre 2016

Dernière vérification

1 novembre 2016

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • IRB00024810

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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