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- Essai clinique NCT01185509
Trastuzumab and Vinorelbine in Advanced Breast Cancer
16 janvier 2019 mis à jour par: Ian E. Krop, MD, PhD, Dana-Farber Cancer Institute
A Phase II, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients With Human Epidermal Growth Factor-2 (HER2) Negative Primary Tumors and HER2 Positive Circulating Tumor Cells
The purpose of this research study is to see what effects trastuzumab in combination with vinorelbine has on breast cancer when the participant has circulating tumor cells that are positive for the protein called HER2.
Trastuzumab is an FDA approved drug that targets HER2.
The drug combination of trastuzumab and vinorelbine is an effective treatment for patients with breast cancers that are positive for HER2.
This trial seeks to determine if the combination can also benefit participants whose original breast cancer was HER2 negative but whose circulating tumor cells are HER2 positive.
Aperçu de l'étude
Statut
Résilié
Les conditions
Intervention / Traitement
Description détaillée
OBJECTIVES:
Primary
- To assess the objective response rate (ORR) of trastuzumab and vinorelbine in patients with metastatic breast cancer with HER2 negative primary tumors and HER2 positive circulating tumor cells.
Secondary
- To describe the number of CTCs and the CTCs characteristics before and after therapy, and to explore the correlation of these findings with response.
- To further characterize the safety and tolerability.
- To evaluate progression-free survival.
- To evaluate clinical benefit rate [complete response (CR)+partial response (PR)+stable disease (SD)>24 weeks].
Exploratory
- To determine the clinical feasibility of high-throughput mutation profiling on circulating tumor cells (CTCs).
Type d'étude
Interventionnel
Inscription (Réel)
31
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
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Massachusetts
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Boston, Massachusetts, États-Unis, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, États-Unis, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, États-Unis, 02115
- Beth Israel Deaconess Medical Center
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-
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:
- Histologically or cytologically confirmed metastatic invasive mammary carcinoma. The primary cancer must be HER2 negative by fluorescence in situ hybridization and/or immunohistochemistry.
- Patients must have CTCs with HER2 amplification by FISH.
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater with conventional techniques of as 10mm or greater with spiral CT scan.
- Study participants must have either archival primary tumor or metastatic tumor tissue available to allow analysis to confirm their HER2 status.
- Patients must have received at least 1 prior chemotherapy regimen for metastatic breast cancer or evidence of disease progression within 6 months of completing adjuvant chemotherapy. Patients can receive any number of biological or hormonal regimens and remain eligible.
- 18 years of age or older
- Life expectancy of greater than 3 months
- ECOG Performance Status of 0, 1 or 2
- Normal organ and marrow function as outlined in the protocol
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
Exclusion Criteria:
- Participants must have recovered from all reversible toxicities related to prior therapy before beginning protocol treatment, and may not have any pre-existing treatment-related toxicities in excess of grade 2
- Participants may not be receiving any other investigational agents while participating in this study
- Participants may not have received trastuzumab or vinorelbine in the past
- Participants receiving any medications or substances that are inhibitors of cytochrome P450 isoenzymes in the CYP3A subfamily are ineligible.
- EKG abnormalities of known clinical significance, such as prolonged QT.
- Left ventricular ejection fraction < 50%
- Patients with peripheral neuropathy of any etiology that exceeds grade 1 are ineligible
- Uncontrolled intercurrent illness
- Individuals with symptomatic or progressive brain metastases are ineligible. Subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for 1 month or longer after completion of local therapy. Any corticosteroid use for brain metastases must have been discontinued without subsequent appearance of symptoms for more than 4 weeks prior to study treatment.
- Individuals with active second malignancy are ineligible. Patients that are disease-free from a previously treated non-breast malignancy and have a 20% or less chance of recurrence are eligible.
- Pregnant or breast feeding women
- HIV-positive individuals on combination antiretroviral therapy
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: Trastuzumab and Vinorelbine - Cohort A
Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity.
Eligibility required patients to have HER2 amplification by fluorescence in situ hybridization (FISH) (mean ratio > 2.0).
The CTC tests of the first 11 patients were done at DFCI.
The study team then decided to proceed with a different CTC test performed outside of DFCI.
Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.
|
Autres noms:
|
Expérimental: Trastuzumab and Vinorelbine - Main Cohort
Cycle 1: Patients received trastuzumab 8 mg/kg intravenously (IV) on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Cycles 2+: Patients received trastuzumab 6 mg/kg IV on day 1 and vinorelbine 25 mg/kg IV on days 1, 8 and 15 of each 21 day cycle Patients were treated until disease progression or unacceptable toxicity.
Eligibility required patients to have HER2 amplification by FISH (mean ratio > 2.0).
The CTC tests of the first 11 patients were done at DFCI.
The study team then decided to proceed with a different CTC test performed outside of DFCI.
Because the method of CTC isolation was different from that performed by DFCI, the first 11 patients were placed into a separate cohort (Cohort A) and the remaining 20 patients represented the main cohort.
|
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Objective Response Rate (ORR)
Délai: Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67).
|
ORR was defined as the percentage of patients achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
|
Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67).
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Clinical Benefit Rate (CBR)
Délai: Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67).
|
CBR was defined as achieving complete response (CR), partial response (PR), or stable disease (SD) for 24 weeks or longer based on RECIST 1.1 criteria on treatment.
Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions.
Stable disease (SD) is defined as any condition not meeting the above criteria.
SD needed to be a minimum 24 weeks in duration
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Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks; Median (range) trt duration was 12 weeks (3-67).
|
Progression-Free Survival (PFS)
Délai: Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks and within 2 wks off-study; Median follow-up was 2.7 months.
|
PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death.
Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase.
For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
|
Disease was evaluated radiologically at baseline, on trt every 6 weeks (wks) for the first 18 wks and then every 12 wks and within 2 wks off-study; Median follow-up was 2.7 months.
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Baseline Level of Circulating Tumor Cells (CTCs)
Délai: Assessed at baseline
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CTCs levels were determined based on established methods.
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Assessed at baseline
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Ian Krop, MD, PhD, Dana-Farber Cancer Institute
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.
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)
1 novembre 2010
Achèvement primaire (Réel)
1 janvier 2017
Achèvement de l'étude (Réel)
1 janvier 2018
Dates d'inscription aux études
Première soumission
18 août 2010
Première soumission répondant aux critères de contrôle qualité
19 août 2010
Première publication (Estimation)
20 août 2010
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
23 janvier 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
16 janvier 2019
Dernière vérification
1 janvier 2019
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies de la peau
- Tumeurs
- Tumeurs par site
- Maladies du sein
- Tumeurs mammaires
- Mécanismes moléculaires de l'action pharmacologique
- Agents antinéoplasiques
- Modulateurs de tubuline
- Agents antimitotiques
- Modulateurs de mitose
- Agents antinéoplasiques phytogéniques
- Agents antinéoplasiques immunologiques
- Trastuzumab
- Vinorelbine
Autres numéros d'identification d'étude
- 10-207
- H4913s (Autre identifiant: Genentech, Inc)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Non
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
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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