- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01939418
Phase Ib/II Trials of RAD001 in Triple Negative Metastatic Breast Cancer
A Phase Ib Trial of Gemcitabine and Cisplatin With RAD001 in Patients With Metastatic Triple Negative Breast Cancer Proceeding to an Open Label Randomized Phase II Trial Comparing Gemcitabine/Cisplatin With or Without RAD001.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
PIK3CA active mutations are the most frequent genetic event in breast cancer, including in TNBC which presents activated PI3K/AKT signaling due to PIK3CA mutation or PTEN deficiency. TNBC cell lines having activated PI3K/AKT signaling showed a high sensitivity to PI3K/mTOR inhibitors. RAD001 is a potent mTOR complex 1 inhibitor and showed to enhance cisplatin or gemcitabine induced apoptosis by inhibiting p53 induced p21 expression.
This study consists of two parts. In a phase Ib part, investigators will explore the recommended dose of gemcitabine, cisplatin, and RAD001 combination in patients with metastatic TNBC. After completing the phase Ib part, investigators will review the data and discuss with Novartis before the start of a phase II part. In the phase II part, investigators will compare the efficacy of the gemcitabine and cisplatin with or without RAD001 in patients with metastatic TNBC.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Lieux d'étude
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Gyeonggido
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Goyangsi, Gyeonggido, Corée, République de, 410-769
- National Cancer Center
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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
Inclusion Criteria:
- Females with histologically confirmed, metastatic or stage IV breast cancer
- ER/PgR negative or poor (Allred score ≤ 3/8) and HER2 negative breast cancer
- ECOG performance status 0-2
- Age ≥ 20 years
- Previously treated by anthracycline and taxane in adjuvant/neoadjuvant or metastatic setting
- ≤ 2 chemotherapy regimens for metastatic disease
- Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.
- CNS metastasis is permitted if asymptomatic and not requiring treatment with steroids and is documented to be non-progressing at study entry
- Presence of measurable or evaluable disease by RECIST 1.1 criteria
- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet ≥100,000/mm3, hemoglobin ≥ 10g/mm3
- Adequate hepatic function: total bilirubin ≤ 1.5 x upper normal limit (UNL), AST/ALT ≤2.5 x UNL or ≤5 x UNL if presented with hepatic metastasis
- Fasting serum cholesterol ≤ 300mg/dl and fasting triglycerides ≤ 2.5 x UNL
- Adequate renal function: Serum creatinine ≤1.5mg/dL
- Patients should sign a written informed consent before study entry
- Patients with positive HBV-DNA of HBsAg at screening must initiate prophylaxis with appropriate antiviral medication at least one week prior to treatment start
Exclusion Criteria:
- Known active CNS metastasis
- Patients who received prior therapy with gemcitabine
- Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
- Patients with more than 3 prior chemotherapy lines for treating metastatic breast cancer.
- Patients who received prior therapy with mTOR inhibitor or PI3K inhibitor
- Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
- Radiotherapy within four weeks prior to enrolment, except radiotherapy to the bone for analgesic purpose or for lytic lesions at risk of fracture. Patients must have recovered from radiotherapy toxicities prior to enrolment.
- Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- Active ulceration of upper gastrointestinal tract
- Other concurrent severe and/or uncontrolled conditions (e.g. uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol.
- Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
- Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A at enrolment (rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) continuously for at least 7 days during any time period in the last 2 weeks prior to enrolment
- Known hypersensitivity to protocol treatment
- Pregnant or breast feeding
- Peripheral neuropathy ≥ grade 2 (NCI CTCAE version 4.0) at randomization
- Patients unwilling to or unable to comply with the protocol
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: RAD001
gemcitabine 800mg/m2, D1 and D8 iv.
every 3 weeks.
cisplatin 30mg/m2, D1 and D8 iv.
every 3 weeks.
RAD001 5mg QD. po.
|
Afinitor 5mg qd. po.
Autres noms:
gemcitabine 800mg/m2 iv.
D1 and D8 every 3 weeks
cisplatin 30mg/m2 iv.
D1 and D8 every 3 weeks
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
The recommended dose of the combination of gemcitabine, cisplatin and RAD001 (everolimus) in patients with metastatic triple-negative breast cancer
Délai: up to 1 year
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phase IB part
|
up to 1 year
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Efficacy of gemcitabine and cisplatin with or without RAD001 in patients with metastatic triple-negative breast cancer by evaluating progression free survival (PFS)
Délai: up to 5 years
|
phase II part
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up to 5 years
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
The maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine/cisplatin/RAD001
Délai: up to 1 year
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phase Ib part
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up to 1 year
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number of patients with adverse events as a measure of safety and tolerability
Délai: up to 5 years
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phase Ib and phase II
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up to 5 years
|
objective response rate
Délai: up to 1 year
|
phase Ib and phase II
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up to 1 year
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Overall survival (OS)
Délai: up to 5 years
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phase Ib and phase II
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up to 5 years
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check biomarkers associated with the response of RAD001: angiogenesis, metabolism, immune cells profiles
Délai: up to 5 years
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phaseIb and phaseII
|
up to 5 years
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: In Hae Park, Doctor, National Cancer Center, Korea
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
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 (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies de la peau
- Tumeurs
- Tumeurs par site
- Maladies du sein
- Tumeurs mammaires
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Gemcitabine
- Évérolimus
Autres numéros d'identification d'étude
- NCCCTS-13-670
- 12491 (Autre identifiant: Korea Food and Drug Administration)
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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