- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00526591
Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer
Randomized Phase II Study of Two Different Doses of RAD-001 (Everolimus) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This randomized phase II trial is studying the side effects and how well everolimus works in treating patients with newly diagnosed localized prostate cancer.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
OBJECTIVES:
Primary
- To determine the clinical effects of everolimus, in terms of pathologic response (i.e., histologic P0, margin status, or capsular penetration) and surgical outcome, in patients with newly diagnosed localized prostate cancer treated with two different doses of everolimus prior to radical prostatectomy.
- To evaluate the safety and tolerability of this drug in these patients.
Secondary
- To determine the effect of this drug on prostate-specific antigen (PSA) levels in these patients.
- To determine the effect of this drug on levels of expression of PTEN, Akt, phospho-mTOR (i.e., Se2448), phospho-p70 S6 kinase (i.e., Thre389), phospho-Smad3 (i.e., Ser433/435), phospho-Smads 1/5 (i.e., Ser463/465), AR, and TUNEL in these patients.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive low-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.
- Arm II: Patients receive high-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.
Within 7 days after the last dose of everolimus, all patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy.
Tumor biopsy specimens acquired prior to treatment and prostate tumor tissue acquired at the time of radical prostatectomy are evaluated for biomarker correlative studies. Tissue samples are assessed by immunohistochemistry (IHC) and tissue microarray analysis for expression of cellular and molecular biomarkers (i.e., p-S6, p-4E-BP1, and p-Akt) that correlate with response. Prostatectomy specimens are also assessed by pathologic analysis for histopathologic response (i.e., pathologic stage, Gleason score, margin status, and tumor size).
After completion of study therapy, patients are followed at 6 weeks.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
-
-
Ohio
-
Cleveland, Ohio, États-Unis, 44195
- Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed newly diagnosed, localized adenocarcinoma of the prostate, meeting any of the following criteria:
- Clinical stage T2a, T2b, T2c, or T3 disease (any grade or PSA)
- Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA)
- Serum PSA ≥ 10 ng/dL (any grade or stage)
- Any stage, PSA, or Gleason score AND ≥ 35% chance of biochemical failure at 5 years based on Kattan's nomogram
- Recommended for radical prostatectomy
- Normal testosterone level
- No pure neuroendocrine or small cell prostate cancer
- No metastatic disease by CT scan, MRI, bone scan, or X-ray
- No clinical evidence of CNS metastases
PATIENT CHARACTERISTICS:
Inclusion criteria:
- ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
- ANC ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Hemoglobin ≥ 8 g/dL
- AST and ALT ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN
- PT/PTT normal (no anticoagulants)
- No active unresolved infection
- No known HIV positivity
- Fertile patients must use effective contraception during and for 6 months after completion of study therapy
Exclusion criteria:
- Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus or temsirolimus) or to its excipients
Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair GI function and alter the absorption of everolimus, including any of the following:
- Ulcerative disease
- Uncontrolled nausea
- Vomiting
- Diarrhea
- Malabsorption syndrome
- Other active malignancy or malignancy at ≥ 30% risk for relapse after completion of therapy, except nonmelanoma skin cancer
Uncontrolled concurrent illness including, but not limited to, any of the following:
- Ongoing or active infection (e.g., bacterial, viral or fungal)
- Severely impaired lung function
- Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)
- Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would limit study compliance
- Any underlying medical condition which, in the principal investigator's opinion, will make the administration of everolimus hazardous OR obscure the interpretation of adverse events
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since major surgery
- More than 3 months since finasteride
- No prior or concurrent radiotherapy to the prostate gland or pelvis
- No prior hormones (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, or antiandrogens [e.g., bicalutamide, flutamide, or nilutamide]) and/or PC-SPES (or PC-x product) or estrogen-containing nutraceuticals
- No prior rapamycin mTOR inhibitor
- No prior small bowel resection that may significantly impair GI function and alter the absorption of everolimus
- No prior or concurrent immunotherapy, chemotherapy, or other investigational therapy for prostate cancer
- No other concurrent investigational or commercial agents
- No other concurrent anticancer agents
- No concurrent, chronic treatment with systemic steroids (except inhaled or topical steroids) or another immunosuppressive agent
- No concurrent live vaccines
- No concurrent strong inhibitors or inducers of the isoenzyme CYP3A administered as systemic therapy
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Low-dose Everolimus Cohort
5mg Everolimus daily continuously for 8 weeks and conventional surgery
|
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
Autres noms:
Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
|
|
Comparateur actif: High-dose Everolimus Cohort
10mg Everolimus daily continuously for 8 weeks and conventional surgery
|
Patients will receive arm-specific dosage of Everolimus daily continuously for 8 week
Autres noms:
Radical prostatectomy with bilateral pelvic lymphadenectomy will be performed within 10 days of the completion of week 8 on RAD-001 (Everolimus).
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery
Délai: After 8 weeks of therapy at the time of prostatectomy
|
Specimens are fixed in formalin for 24 hours.Specimens are the cut at 3 mm intervals perpendicular to the rectal surface and the sections are examined grossly and microscopically on routine Hematoxylin and Eosin stain (H&E) (pathologic complete response or P0) will be defined as responders.
|
After 8 weeks of therapy at the time of prostatectomy
|
|
Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity)
Délai: at daily dose for 8 weeks
|
Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0)
|
at daily dose for 8 weeks
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change in PSA
Délai: Up to 16 weeks after start of study
|
Time-to-event data, such as change in PSA will be summarized using the method of Kaplan and Meier.
|
Up to 16 weeks after start of study
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Effect of Treatment on Biological and Molecular Markers
Délai: After 8 weeks of therapy
|
Immunohistochemical Staining of Cellular and Molecular Markers in Prostate Tumor Tissue
|
After 8 weeks of therapy
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Jorge A. Garcia, MD, Case Comprehensive Cancer Center
Publications et liens utiles
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 (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- CASE21806
- P30CA043703 (Subvention/contrat des NIH des États-Unis)
- CASE-21806 (Autre identifiant: Case Comprehensive Cancer Center)
- CASE-21806-CC256 (Autre identifiant: Cancer Center IRB)
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
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 .