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

26 marca 2019 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

143

Faza

  • Faza 4

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Afryka Południowa
      • Cape Town, Afryka Południowa, 7500
        • Novartis Investigative Site
      • Cape Town, Afryka Południowa, 7925
        • Novartis Investigative Site
      • Durban, Afryka Południowa, 4001
        • Novartis Investigative Site
      • Parktown, Afryka Południowa, 2193
        • Novartis Investigative Site
  • Algieria
      • Alger, Algieria, 016000
        • Novartis Investigative Site
      • Oran, Algieria
        • Novartis Investigative Site
  • Arabia Saudyjska
      • Riyadh, Arabia Saudyjska, 11211
        • Novartis Investigative Site
  • Egipt
      • Alexandria, Egipt, 21131
        • Novartis Investigative Site
      • Cairo, Egipt
        • Novartis Investigative Site
      • Mansoura, Egipt
        • Novartis Investigative Site
  • Federacja Rosyjska
      • Moscow, Federacja Rosyjska, 115478
        • Novartis Investigative Site
      • Samara, Federacja Rosyjska, 443031
        • Novartis Investigative Site
  • Indie
    • Madhya Pradesh
      • Indore, Madhya Pradesh, Indie, 452 008
        • Novartis Investigative Site
    • Maharashtra
      • Pune, Maharashtra, Indie, 411013
        • Novartis Investigative Site
  • Jordania
      • Amman, Jordania, 11941
        • Novartis Investigative Site
  • Liban
      • Ashrafieh, Liban, 166830
        • Novartis Investigative Site
  • Tajlandia
      • Bangkok, Tajlandia, 10400
        • Novartis Investigative Site
      • Chiang Mai, Tajlandia, 50200
        • Novartis Investigative Site
    • Hat Yai
      • Songkhla, Hat Yai, Tajlandia, 90110
        • Novartis Investigative Site
  • Tunezja
      • Ariana, Tunezja, 2080
        • Novartis Investigative Site
      • Sousse, Tunezja, 4000
        • Novartis Investigative Site
    • Tunisie
      • Tunis, Tunisie, Tunezja, 1007
        • Novartis Investigative Site

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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 studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nielosowe
  • Model interwencyjny: Zadanie dla jednej grupy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: RAD001
Lek: RAD001
Inne nazwy:
  • Ewerolimus

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
PFS (Progression-Free Survival)
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Disease Control Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]);
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Novartis Pharmaceuticals

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

11 listopada 2009

Zakończenie podstawowe (Rzeczywisty)

6 czerwca 2017

Ukończenie studiów (Rzeczywisty)

1 lipca 2017

Daty rejestracji na studia

Pierwszy przesłany

21 września 2010

Pierwszy przesłany, który spełnia kryteria kontroli jakości

21 września 2010

Pierwszy wysłany (Oszacować)

22 września 2010

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

24 czerwca 2019

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

26 marca 2019

Ostatnia weryfikacja

1 marca 2019

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • CRAD001LIC01

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Opis planu 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

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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