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A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.

26 mars 2019 mis à jour par: Novartis Pharmaceuticals

An Open-label, Multi-center Phase 2 Study to Evaluate Everolimus as Monotherapy Treatment for Patients With Metastatic Recurrent and/or Unresectable Renal Cell Carcinoma (EVERMORE).

Renal cell carcinoma (RCC) accounts for more than 200,000 new cases of cancer and over 100,000 cancer deaths annually in the World (Ferlay, et al., 2004). It is estimated that there were about 15,000 new cases of RCC in the region that excludes the Americas, European Union and Japan. Renal cell carcinomas arise from the proximal tubal epithelium are more common in males than in females with an overall lifetime risk of 1 in 75 and a median age of diagnosis of 65 years.

Everolimus (Certican®) has been approved since 2003 in more than 60 countries for the prevention of organ rejection in patients with renal and cardiac transplantation. Everolimus (RAD001) is a derivative of rapamycin, which acts as a signal transduction inhibitor. It targets mTOR, a key protein kinase regulating cell growth, proliferation, and survival. The mTOR pathway activity is modulated by the phosphatidylinositol-3-kinase (PI3K)/protein kinase B AKT (AKT) pathway, a pathway known to be deregulated in numerous human cancers. RAD001 (Afinitor®) has been investigated as an anticancer agent based on its potential to act:

  • directly on the tumor cells by inhibiting tumor cell growth and proliferation;
  • indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell hypoxia-inducible factor 1 (HIF-1) activity, VEGF production, and VEGF-induced proliferation of endothelial cells).

Primary: To evaluate the PFS rate over time.

Secondary:

  • To evaluate the disease control rate (stable disease [SD] + partial response [PR] + complete response [CR]);
  • To evaluate the objective response rate (ORR; where ORR = CR + PR) and duration;
  • To describe the safety profile of RAD001.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

143

Phase

  • Phase 4

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

  • Afrique du Sud
      • Cape Town, Afrique du Sud, 7500
        • Novartis Investigative Site
      • Cape Town, Afrique du Sud, 7925
        • Novartis Investigative Site
      • Durban, Afrique du Sud, 4001
        • Novartis Investigative Site
      • Parktown, Afrique du Sud, 2193
        • Novartis Investigative Site
  • Algérie
      • Alger, Algérie, 016000
        • Novartis Investigative Site
      • Oran, Algérie
        • Novartis Investigative Site
  • Arabie Saoudite
      • Riyadh, Arabie Saoudite, 11211
        • Novartis Investigative Site
  • Egypte
      • Alexandria, Egypte, 21131
        • Novartis Investigative Site
      • Cairo, Egypte
        • Novartis Investigative Site
      • Mansoura, Egypte
        • Novartis Investigative Site
  • Fédération Russe
      • Moscow, Fédération Russe, 115478
        • Novartis Investigative Site
      • Samara, Fédération Russe, 443031
        • Novartis Investigative Site
  • Inde
    • Madhya Pradesh
      • Indore, Madhya Pradesh, Inde, 452 008
        • Novartis Investigative Site
    • Maharashtra
      • Pune, Maharashtra, Inde, 411013
        • Novartis Investigative Site
  • Jordan
      • Amman, Jordan, 11941
        • Novartis Investigative Site
  • Liban
      • Ashrafieh, Liban, 166830
        • Novartis Investigative Site
  • Thaïlande
      • Bangkok, Thaïlande, 10400
        • Novartis Investigative Site
      • Chiang Mai, Thaïlande, 50200
        • Novartis Investigative Site
    • Hat Yai
      • Songkhla, Hat Yai, Thaïlande, 90110
        • Novartis Investigative Site
  • Tunisie
      • Ariana, Tunisie, 2080
        • Novartis Investigative Site
      • Sousse, Tunisie, 4000
        • Novartis Investigative Site
    • Tunisie
      • Tunis, Tunisie, Tunisie, 1007
        • Novartis Investigative Site

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: Patients may be entered in the study only if they meet all of the following criteria:

  • Age ≥18 years old;
  • Patients with advanced renal cell carcinoma with confirmed clear or non-clear cell histology, with or without nephrectomy, and with any MSKCC prognosis;
  • Prior cytokine therapy is permitted;
  • Patients with at least one measurable lesion at baseline as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. If skin lesions are reported as target lesions, they must be documented (at baseline and at every physical exam) using color photography and a measuring device (such as a caliper) in clear focus to allow the size of the lesion(s) to be determined from the photograph;
  • Life expectancy ≥3 months. Life expectancy should be judged in relation to other determining patient eligibility factors such as laboratory results, Karnofsky Performance Status, etc.;
  • Patients with a Karnofsky Performance Status ≥70%;
  • Adequate bone marrow function as shown by: absolute neutrophil count (ANC) ≥1.5 x 109/L, platelets ≥100 x 109/L, hemoglobin (Hb) >9 g/dL;
  • Adequate liver function: serum bilirubin ≤1.5 x upper limit of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5 x ULN;
  • Adequate renal function: serum creatinine ≤1.5 x ULN;
  • Females of childbearing potential must have had a negative serum or urine pregnancy test 7 days prior to the administration of the study treatment start;
  • Patients who give a written informed consent obtained according to local guidelines.

Exclusion Criteria:Patients may not be entered into the study if they meet any of the following criteria:

  • Patients within 2 weeks post-minor surgery (e.g., herniorrhaphy), 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal, or intra-pelvic) to avoid wound healing complications. Percutaneous biopsies require no waiting time prior to study entry;
  • Patients with a recent history of hemoptysis, ≥0.5 teaspoon of red blood;
  • Patients who have received prior systemic treatment for their metastatic RCC other than with cytokine therapy;
  • Patients who received prior therapy with a VEGF pathway inhibitor, such as sunitinib, sorafenib, and bevacizumab;
  • Patients who have previously received mTOR inhibitors (sirolimus, temsirolimus, everolimus, deferolimus);
  • History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:

Are asymptomatic; Have had no evidence of active CNS metastases for ≥6 months prior to enrollment and; Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC);

• Clinically significant gastrointestinal abnormalities including, but not limited to: Malabsorption syndrome; Major resection of the stomach or small bowel that could affect the absorption of study drug; Active peptic ulcer disease; Inflammatory bowel disease; Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning of study treatment;

  • Patients receiving chronic systemic treatment with corticosteroids (dose of ≥10 mg/day methylprednisone equivalent) or another immune-suppressive agent. Inhaled and topical steroids are acceptable, as well as opotherapy after bilateral adrenal gland removal;
  • Patients with a known history of human immunodeficiency virus seropositivity;
  • Patients with autoimmune hepatitis;
  • Patients with an active, bleeding diathesis. Patients may use coumadin or heparin preparations;
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study;
  • Patients who have a history of another primary malignancy ≤3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine;
  • Female patients who are pregnant or breastfeeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the study by both sexes. Oral contraceptives are not acceptable;
  • Patients who are using other investigational agents or who had received investigational drugs ≤4 weeks prior to study treatment start; Patients unwilling or unable to comply with the protocol.

Other protocol-defined inclusion/exclusion may apply

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 à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: RAD001
Médicament: RAD001
Autres noms:
  • Évérolimus

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
PFS (Progression-Free Survival)
Délai: Approximately 4 years
the time from the date of the start of RAD001 treatment to the date of the first documented disease progression or death due to any cause
Approximately 4 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Disease Control Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]);
Délai: Approximately 4 years
The disease control rate was based on the data as per local radiological review following the RECIST criteria. The disease control rate is defined as the proportion of patients with CR, PR, or SD and was summarized in terms of percentage with 95% exact Clopper-Pearson CIs
Approximately 4 years
Objective Response Rate (ORR; Where ORR = CR + PR)
Délai: Approximately 4 years
The overall tumor response was based on the data as per local radiological review, following RECIST criteria. The ORR is defined as the proportion of patients with CR or PR and was summarized in terms of percentage with 95% exact Clopper-Pearson CIs
Approximately 4 years
Duration of Response (DOR)
Délai: Approximately 4 years
The DOR analysis applied only to patients whose overall response was CR or PR and was defined as the time from onset of response (CR/PR) to progression or death from any cause
Approximately 4 years
Overall Survival
Délai: Approximately 4 years
Overall survival is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.
Approximately 4 years

Collaborateurs et enquêteurs

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

Parrainer

Novartis Pharmaceuticals

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 (Réel)

11 novembre 2009

Achèvement primaire (Réel)

6 juin 2017

Achèvement de l'étude (Réel)

1 juillet 2017

Dates d'inscription aux études

Première soumission

21 septembre 2010

Première soumission répondant aux critères de contrôle qualité

21 septembre 2010

Première publication (Estimation)

22 septembre 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

24 juin 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

26 mars 2019

Dernière vérification

1 mars 2019

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CRAD001LIC01

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Description du régime IPD

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

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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