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A Study of GDC-0941 in Participants With Locally Advanced or Metastatic Solid Tumors for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable

1 novembre 2016 mis à jour par: Genentech, Inc.

An Open-Label, Phase I, Dose-Escalation Study Evaluating Two Dosing Schedules of PI3-Kinase Inhibitor (GDC-0941) in Patients With Locally Advanced or Metastatic Solid Tumors for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable

This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of orally administered GDC-0941 administered once daily (QD) and twice daily (BID) in the treatment of advanced or metastatic solid tumors.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

108

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

    • Arizona
      • Scottsdale, Arizona, États-Unis, 85258
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02215
    • Michigan
      • Detroit, Michigan, États-Unis, 48201

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:

  • Participants with histologically documented, incurable, locally advanced or metastatic solid malignancy that has progressed or failed to respond to at least one prior regimen, and who are not candidates for regimens known to provide clinical benefit
  • Evaluable or measurable disease per RECIST
  • Life expectancy of greater than or equal to (>/=) 12 weeks
  • Documented willingness to use an effective means of contraception (for both men and women) while participating in the study

Exclusion Criteria:

  • Leptomeningeal disease as the only manifestation of the current malignancy
  • History of Type 1 or 2 diabetes mellitus requiring regular medication
  • Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytics
  • Malabsorption syndrome or other condition that would interfere with enteral absorption
  • Known untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for >/=3 months
  • Active congestive heart failure or ventricular arrhythmia requiring medication
  • Uncontrolled ascites requiring weekly large-volume paracentesis for 3 consecutive weeks prior to enrollment
  • Active infection requiring intravenous (IV) antibiotics
  • Requirement for any daily supplemental oxygen
  • Uncontrolled hypomagnesemia or hypokalemia, defined as values below the lower limit of normal (LLN), or hypercalcemia above the upper limit of normal (ULN) for the institution despite adequate electrolyte supplementation or management
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Known human immunodeficiency virus (HIV) infection
  • Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high risk from treatment complications
  • Significant traumatic injury within 3 weeks before Day 1
  • Major surgical procedure within 4 weeks prior to initiation of study treatment
  • Treatment with chemotherapy, hormonal therapy (except gonadotropin releasing hormone [GnRH] agonists or antagonists for prostate cancer), immunotherapy, biologic therapy, or radiation therapy (except palliative radiation to bony metastases) as cancer therapy within 4 weeks prior to initiation of study treatment
  • Palliative radiation to bony metastases within 2 weeks prior to initiation of study treatment
  • Need for chronic corticosteroid therapy for greater than (>) 7 days

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
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Group A: GDC-0941 QD Dose Escalation
Participants will receive GDC-0941 for up to 1 year, administered orally QD at a starting dose of 15 milligrams (mg).
GDC-0941 will be administered in escalating oral doses QD or BID in Groups A and B, respectively. In Group C, the dose/regimen will be determined on the basis of data from Groups A and B. The overall starting dose will be 15 mg administered in the first cohort enrolled in Group A.
Autres noms:
  • PI3-Kinase Inhibitor
Expérimental: Group B: GDC-0941 BID Dose Escalation
Participants will receive GDC-0941 for up to 1 year, administered orally BID at a starting dose determined from Group A assessments.
GDC-0941 will be administered in escalating oral doses QD or BID in Groups A and B, respectively. In Group C, the dose/regimen will be determined on the basis of data from Groups A and B. The overall starting dose will be 15 mg administered in the first cohort enrolled in Group A.
Autres noms:
  • PI3-Kinase Inhibitor
Expérimental: Group C: GDC-0941 QD or BID Expansion
Participants will receive GDC-0941 for up to 1 year, administered orally QD or BID. The dose/regimen will be determined on the basis of data from Groups A and B.
GDC-0941 will be administered in escalating oral doses QD or BID in Groups A and B, respectively. In Group C, the dose/regimen will be determined on the basis of data from Groups A and B. The overall starting dose will be 15 mg administered in the first cohort enrolled in Group A.
Autres noms:
  • PI3-Kinase Inhibitor

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Maximum Observed Concentration (Cmax) of GDC-0941
Délai: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Terminal Elimination Half-Life (t1/2) of GDC-0941
Délai: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Area Under the Concentration-Time Curve (AUC) of GDC-0941
Délai: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Percentage of Participants with Adverse Events
Délai: Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Délai: Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36
Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36
Percentage of Participants with Grade 3 or 4 Abnormalities in Safety-Related Laboratory Parameters
Délai: Visits at Baseline and during treatment on Days 1, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
Visits at Baseline and during treatment on Days 1, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
Time of Maximum Observed Concentration (Tmax) of GDC-0941
Délai: Pre-dose (5 minutes [min]) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 hours [h]) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Pre-dose (5 minutes [min]) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 hours [h]) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)

Mesures de résultats secondaires

Mesure des résultats
Délai
Duration of Objective Response According to RECIST
Délai: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
Progression-Free Survival (PFS) According to RECIST
Délai: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
Percentage of Participants by Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)
Délai: Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)
Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall)

Collaborateurs et enquêteurs

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

Parrainer

Les enquêteurs

  • Directeur d'études: Jerry Hsu, M.D., Genentech, Inc.

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 octobre 2007

Achèvement primaire (Réel)

1 juin 2012

Achèvement de l'étude (Réel)

1 novembre 2013

Dates d'inscription aux études

Première soumission

13 mars 2009

Première soumission répondant aux critères de contrôle qualité

3 avril 2009

Première publication (Estimation)

6 avril 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

2 novembre 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

1 novembre 2016

Dernière vérification

1 novembre 2016

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • GDC4255g
  • GO01300 (Autre identifiant: Hoffmann-La Roche)

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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