- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01313390
Everolimus and Docetaxel in Treating Patients With Recurrent, Locally Advanced, or Metastatic Head and Neck Cancer (DORA)
DORA: A Phase I and Randomized Phase II Study of Docetaxel and RAD001 (Everolimus) in Advanced/Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving everolimus together with docetaxel is more effective than giving docetaxel alone in treating patients with head and neck cancer.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus given together with docetaxel in treating patients with recurrent, locally advanced, or metastatic head and neck cancer.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
OBJECTIVES:
Primary
- To determine the safety and tolerability of the combination of everolimus and docetaxel in treating patients with recurrent, locally advanced or metastatic squamous cell carcinoma of the head and neck. (Phase I)
- To determine the maximum-tolerated dose and recommended phase II dose of everolimus when combined with docetaxel in these patients. (Phase I)
- To examine the response rates in patients receiving the combination of docetaxel and everolimus and those receiving docetaxel alone. (Phase II)
Secondary
- To investigate possible pharmacokinetic interactions between docetaxel and everolimus in these patients. (Phase I)
- To investigate the effect of everolimus on downstream targets of mTOR in tumor in these patients. (Phase I)
- To examine the time to progression after docetaxel and everolimus in these patients. (Phase II)
- To perform a pilot study to attempt to identify predictors of response, including evaluation of EGFR family member expression, mutations, or amplifications. (Phase II)
- To attempt to identify downstream targets of the EGFR pathway including phosphorylation of S6 and phosphorylation of AKT. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of everolimus with docetaxel followed by a randomized phase II study.
- Phase I: Patients receive docetaxel IV over 1 hour on day 1 and escalating doses of oral everolimus on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses of therapy, patients may continue to receive everolimus weekly as a single agent until evidence of progressive disease.
Phase II: Patients are randomized to 1 of 2 treatment arms:
- Arm A: Patients receive docetaxel IV over 1 hour on day 1.Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with progressive disease are eligible to cross over into the everolimus arm at the investigator's discretion.
- Arm B: Patients receive docetaxel as in arm A and oral everolimus (at a dose determined in the phase I portion of the study) on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the completion of combination therapy, patients may continue to receive maintenance everolimus weekly, at the investigator's discretion.
Blood samples are collected for pharmacokinetic monitoring in the phase I study. Tissue samples are collected at baseline and periodically during the study for biomarker and other laboratory analysis.
After completion of study treatment, patients are followed up every 3 months for at least 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
PROJECTED ACCRUAL: Approximately 18 patients will be accrued for phase I and a total of 100 patients will be accrued for phase II of this study.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Lieux d'étude
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England
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London, England, Royaume-Uni, WC1E 6DD
- UCL Cancer Institute
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
DISEASE CHARACTERISTICS:
Histologically confirmed squamous cell carcinoma of the head and neck
Locally advanced or metastatic disease
- No patients with locally advanced disease for whom radiotherapy is indicated
- Recurrent disease
- Incurable disease
Measurable disease by RECIST criteria
- Recurrent disease within a prior radiation field can be considered to be measurable
- Patients may have received 1 line of prior chemotherapy (but not a taxane) for locally advanced or metastatic disease
Patients may have received prior radiation therapy for locally advanced or metastatic disease (but must have completed the radiotherapy > 6 months before recruitment)
- No disease relapsed within 6 months of radiotherapy
- No evidence of central nervous system metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Life expectancy ≥ 12 weeks
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10 g/dL
- Urea and creatinine normal
- Serum bilirubin normal
- AST or ALT ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase < 2.5 times ULN
- Negative pregnancy test
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 3 months (female) or 2 months (male) after the last dose of the study treatment
- No uncontrolled infection
- No mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study
- No prior malignancy likely to interfere with the patient's ability to comply with treatment and/or follow up
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy for any cancer, except for head and neck cancer
- No prior taxane
- No prior therapy with any erbB inhibitors (except cetuximab given with radiotherapy, as indicated in treatment algorithm)
- More than 6 months since prior radiotherapy for locally advanced or metastatic disease
- At least 4 weeks since prior investigational drug
- No concurrent use of drugs known to inhibit CYP3A4 (except dexamethasone), or block P-glycoprotein, including grapefruit juice
- No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or experimental medications
- No concurrent live vaccines during everolimus therapy
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
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Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I)
|
Safety and tolerability of the combination of everolimus and docetaxel
|
Response using RECIST criteria (phase II)
|
Mesures de résultats secondaires
Mesure des résultats |
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Pharmacokinetic profile of docetaxel with and without concurrent everolimus (phase I)
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Pharmacokinetic profile of everolimus with and without concurrent docetaxel (phase I)
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Time to progression following response (time from treatment start to tumor progression as defined by RECIST criteria) (phase II)
|
Mutations in EGFR1, AKT, mTOR, ras, or p53 to be tested on paraffin-embedded tissue from the primary or secondary tumor; results to be correlated with outcome (phase II)
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Amplifications of EGFR1 and bcl2 expression to be tested by FISH and immunostaining on paraffin-embedded tissue from primary tumor; results to be correlated with outcome (phase II)
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Chris Boshoff, University College London (UCL) Cancer Institute
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
- cancer épidermoïde métastatique récurrent du cou avec primitif occulte
- cancer épidermoïde du cou métastatique avec carcinome épidermoïde primitif occulte
- carcinome épidermoïde de stade III de la lèvre et de la cavité buccale
- carcinome verruqueux stade III de la cavité buccale
- carcinome épidermoïde de stade IV de la lèvre et de la cavité buccale
- carcinome verruqueux stade IV de la cavité buccale
- carcinome épidermoïde récurrent de la lèvre et de la cavité buccale
- carcinome verruqueux récurrent de la cavité buccale
- carcinome épidermoïde stade III de l'oropharynx
- carcinome épidermoïde stade IV de l'oropharynx
- carcinome épidermoïde récurrent de l'oropharynx
- carcinome épidermoïde de stade III du nasopharynx
- carcinome épidermoïde de stade IV du nasopharynx
- carcinome épidermoïde récurrent du nasopharynx
- carcinome épidermoïde de stade III de l'hypopharynx
- carcinome épidermoïde de stade IV de l'hypopharynx
- carcinome épidermoïde récurrent de l'hypopharynx
- carcinome épidermoïde de stade III du larynx
- carcinome verruqueux stade III du larynx
- carcinome épidermoïde de stade IV du larynx
- carcinome verruqueux stade IV du larynx
- carcinome épidermoïde récurrent du larynx
- carcinome verruqueux récurrent du larynx
- carcinome épidermoïde de stade III du sinus paranasal et de la cavité nasale
- carcinome épidermoïde de stade IV du sinus paranasal et de la cavité nasale
- carcinome épidermoïde récurrent du sinus paranasal et de la cavité nasale
- cancer récurrent des glandes salivaires
- cancer des glandes salivaires stade III
- cancer des glandes salivaires de stade IV
- cancer de la langue
- carcinome épidermoïde des glandes salivaires
Termes MeSH pertinents supplémentaires
- Tumeurs
- Tumeurs par site
- Tumeurs de la tête et du cou
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Modulateurs de tubuline
- Agents antimitotiques
- Modulateurs de mitose
- Docétaxel
- Évérolimus
Autres numéros d'identification d'étude
- CDR0000696702
- CRUK-UCL-06/053
- EU-20959
- ISRCTN-73814534
- EUDRACT-2007-001951-20
- CRUK-UCL-CTA-20363/0229/011-00
- NOVARTIS-CRUK-UCL-06/053
- AVENTIS-CRUK-UCL-06/053
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 .
Essais cliniques sur Cancer de la tête et du cou
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