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PF-04856884 (CVX-060) In Combination With Axitinib In Patients With Previously Treated Metastatic Renal Cell Carcinoma

19 décembre 2018 mis à jour par: Pfizer

A PHASE II TRIAL OF PF-04856884 (CVX-060), A SELECTIVE ANGIOPOIETIN-2 (ANG-2) INHIBITOR IN COMBINATION WITH AG-013736 (AXITINIB) IN PATIENTS WITH PREVIOUSLY TREATED METASTATIC RENAL CELL CARCINOMA

To evaluate the combination of PF-04856884 (CVX-060) in combination with Axitinib (AG-013736) in patients that have received one prior systemic regimen for metastatic renal cell carcinoma (mRCC) vs. axitinib alone.

Aperçu de l'étude

Statut

Résilié

Les conditions

Intervention / Traitement

Description détaillée

The study was prematurely discontinued on 06Nov2012 due to tolerability findings in patients treated in Part I of the study that have prompted the Sponsor to re-evaluate the strategic development of the program. An unexpected frequency of arterial thrombotic events (ATEs) and venous thrombotic events (VTEs) were reported in patients treated in Part I.

Type d'étude

Interventionnel

Inscription (Réel)

18

Phase

  • Phase 2

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

  • Tchéquie
      • Brno, Tchéquie, 65653
        • Masarykuv Onkologicky Ustav
  • États-Unis
    • Arizona
      • Scottsdale, Arizona, États-Unis, 85258
        • Pinnacle Oncology Hematology
      • Tucson, Arizona, États-Unis, 85704
        • Arizona Oncology Associates, PC - HOPE
      • Tucson, Arizona, États-Unis, 85710
        • Arizona Oncology Associates, PC-Hope
    • Colorado
      • Aurora, Colorado, États-Unis, 80012
        • Rocky Mountain Cancer Centers
      • Boulder, Colorado, États-Unis, 80303
        • Rocky Mountain Cancer Centers
      • Centennial, Colorado, États-Unis, 80112
        • Rocky Mountain Cancer Centers
      • Colorado Springs, Colorado, États-Unis, 80907
        • Rocky Mountain Cancer Centers
      • Colorado Springs, Colorado, États-Unis, 80909
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, États-Unis, 80218
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, États-Unis, 80220
        • Rocky Mountain Cancer Centers
      • Lakewood, Colorado, États-Unis, 80228
        • Rocky Mountain Cancer Centers
      • Littleton, Colorado, États-Unis, 80120-4413
        • Rocky Mountain Cancer Centers
      • Lone Tree, Colorado, États-Unis, 80124
        • Rocky Mountain Cancer Centers
      • Longmont, Colorado, États-Unis, 80501
        • Rocky Mountain Cancer Centers
      • Parker, Colorado, États-Unis, 80138
        • Rocky Mountain Cancer Centers
      • Pueblo, Colorado, États-Unis, 81008
        • Rocky Mountain Cancer Centers
      • Thornton, Colorado, États-Unis, 80260
        • Rocky Mountain Cancer Centers
    • Nebraska
      • Omaha, Nebraska, États-Unis, 68114
        • Nebraska Methodist Hospital
    • Nevada
      • Henderson, Nevada, États-Unis, 89074
        • Comprehensive Cancer Centers of Nevada
      • Henderson, Nevada, États-Unis, 89052
        • Comprehensive Cancer Centers of Nevada
      • Henderson, Nevada, États-Unis, 89014
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, États-Unis, 89148
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, États-Unis, 89128
        • Comprehensive Cancer Centers of Nevada
      • Las Vegas, Nevada, États-Unis, 89169
        • Comprehensive Cancer Centers of Nevada
    • North Carolina
      • Durham, North Carolina, États-Unis, 27704
        • Regional Cancer Care-Durham
    • Texas
      • Tyler, Texas, États-Unis, 75702
        • Texas Oncology-Tyler
    • Washington
      • Seattle, Washington, États-Unis, 98109
        • Seattle Cancer Care Alliance
      • Seattle, Washington, États-Unis, 98195
        • University of Washington Medical 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 et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Adult male or female patients with histologically or cytologically confirmed renal cell cancer (RCC) with a component of clear cell subtype and evidence of metastasis
  • Evidence of unidimensionally measurable disease
  • Prior therapy: Part I: Having received 1 to 3 prior systemic regimens for treatment of mRCC
  • Part II: Evidence of disease progression following 1 prior regimen administered as 1st line therapy for mRCC. The prior regimen must have contained one of the following: VEGFR2 tyrosine kinase inhibitor (TKI) or other anti VEGF [Vascular Endothelial Growth Factor] compounds, such as bevacizumab
  • adequate bone marrow, liver and renal function

Exclusion Criteria:

Part I:

  • Intolerant to prior AG 013736 therapy or prior treatment with compounds which contain the core platform antibody as PF 04856884

Part II:

  • Prior AG 013736 therapy, more than one systemic first-line regimen for the treatment of mRCC and prior treatment with compounds which contain the core platform antibody as PF 04856884
  • major surgery <4 weeks or radiation therapy <2 weeks prior to start of therapy
  • clinically significant gastrointestinal abnormalities
  • current use or anticipated need for drugs that are known potent CYP3A4 inhibitors and drugs that are known CYP3A4 or CYP1A2 inducers
  • history of bleeding diathesis or coagulopathy
  • Grade 3 or greater hemorrhage from any cause <4 weeks prior to screening;
  • hemoptysis >½ teaspoon of blood per day within 2 weeks prior to screening.

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: Randomisé
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: ARM A
PF-04856884 in combination with AG-013736
Biologique: PF-04856884
15 mg/kg/week intravenously [IV] until toxicity or disease progression
Médicament: Axitinib (AG-013736)
5 mg PO BID
Comparateur actif: ARM B
AG-013736 alone
Médicament: Axitinib (AG-013736)
5 mg PO BID

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Non-serious Adverse Events (AEs) in Part I (Reported in ≥2 of the Participants Overall).
Délai: 4 months

Incidence and severity of all treatment-emergent AEs (TEAEs) of both all-causality and treatment-related by preferred term (PT) categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades reported in ≥2 participants overall (CTCAE Grades 3, 4 and 5, combined) for any PT are presented. Participants who are included under all-causality TEAE PT are coded as NA if they appear for the same PT under treatment-related TEAE below.

Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
4 months
Number of Participants With Serious Adverse Events (SAEs) in Part I
Délai: 4 months
Incidence and severity of all-causality serious adverse events (SAEs) are presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week). Participants with treatment-related TEAE are coded as NA if they appear for the same preferred term under all-causality TEAE.
4 months
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) in Part II
Délai: 3 years
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. Progression free survival was to be calculated as (first event date - the date of randomization +1).
3 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of Participants With Non-serious AEs and SAEs
Délai: 3 years
Incidence and severity of all-causality AEs and SAEs to be presented by PT categorized according to Common Terminology Criteria for Adverse Events (CTCAE) grades. Participants in Part I received PF-04856884 15 mg/kg/week and AG-013736 5 mg twice daily. Following the decision on 06 November 2012 not to continue with Part II of the study, any participant remaining in Part I continued to receive PF-04856884 at a reduced dose of 10 mg/kg/week in combination with AG-013736 (5 mg twice a week) or AG-013736 alone (5 mg twice a week).
3 years
Overall Response Rate (ORR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone.
Délai: 4 months
ORR is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), relative to all randomized participants as defined in the FA Set. Confirmed responses are those that persist on repeat imaging study ≥ 4 weeks after initial documentation of response. Participants who do not have on-study radiographic tumor evaluation or who die, progress, or drop out for any reason prior to reaching a CR or PR will be counted as non-responders (NR) in the assessment of ORR.
4 months
Duration of Response (DR) in Metastatic Renal Cell Cancer (mRCC) Patients Treated With PF-04856884 in Combination With AG-013736 vs. AG-013736 Alone
Délai: 3 years
DR is defined as the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of tumor progression or to death due to cancer. Duration of tumor response was to be calculated as (the end date for DR - first CR or PR that is subsequently confirmed +1).
3 years
Tmax (Time When Maximum Serum PF-04856884 Concentration Was Reached)
Délai: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Pharmacokinetic parameter, Tmax (Time when maximum serum PF-04856884 concentration was reached) was done using non-compartmental methods.
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Cmax (Observed Peak Serum PF-04856884 Concentration)
Délai: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Pharmacokinetic parameter Cmax (observed peak PF-04856884 serum concentration) was estimated using noncompartmental methods.
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Cmin (Trough PF-04856884 Serum Concentration)
Délai: Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Pharmacokinetic parameter Cmin (trough PF-04856884 serum concentration) was estimated using noncompartmental methods.
Pre-dose, 1, 2, 4, 6, 8, 192, 360, 361, 362, 365, 367 hours post dose and end of treatment
Number of Anti-drug Antibodies (ADA) Samples Confirmed Positive
Délai: 0 and 360 hours post dose and end of study
Detection of neutralizing anti-PF-04856884 antibodies was based on the ability of anti-PF-04856884 neutralizing antibodies to bind to Tag-PF-04856884.
0 and 360 hours post dose and end of study
Progression Free Survival (PFS) in Adult Participants With Previously Treated Metastatic Renal Cell Cancer (mRCC) as Measured by an Independent Radiological Assessment
Délai: 3 years
PFS is defined as the time (in days) from date of randomization to first documentation of investigator assessed tumor progression or death, whichever comes first. PFS was to be calculated as (first event date - the date of randomization +1).
3 years
Overall Survival (OS) at 2 Years
Délai: 5 years
OS is defined as the time from the first dose date to date of death. For participants not expiring, their survival times will be censored at the last date they are known to be alive, or 2 year whichever is earlier. The 2-year OS rate will be estimated from a time-to event analysis of OS.
5 years

Collaborateurs et enquêteurs

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

Parrainer

Pfizer

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Liens utiles

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)

21 novembre 2011

Achèvement primaire (Réel)

27 mars 2014

Achèvement de l'étude (Réel)

27 mars 2014

Dates d'inscription aux études

Première soumission

26 août 2011

Première soumission répondant aux critères de contrôle qualité

23 septembre 2011

Première publication (Estimation)

27 septembre 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

8 janvier 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

19 décembre 2018

Dernière vérification

1 décembre 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • B1131004
  • 2011-002190-33 (Numéro EudraCT)

Plan pour les données individuelles des participants (IPD)

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

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Description du régime IPD

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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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