- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02478125
Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
A Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
This is an open label, multiple site, pilot study. Hypothesis: Treatment with Burixafor hydrobromide will effectively mobilize metastatic prostate cancer (PCa) cells (i.e. disseminated tumor cells; DTCs) into the blood from the bone marrow. In preclinical models, these bone marrow niche engaged cells are more resistant to therapy as compared to soft tissue sites.
It has been demonstrated that prostate cancer cells have been mobilized out of the bone marrow of mice utilizing an anti-CXCR4 strategy; making them more susceptible to chemotherapy. Currently, the anti-CXCR4 agent plerixafor is FDA approved to be given for up to 4 consecutive days in order to mobilize hematopoietic stem cells (HSCs).
Burixafor hydrobromide is a potent anti-CXCR4 agent that is in clinical trials. Burixafor hydrobromide, alone or in combination with G-CSF, is currently in Phase II testing for use as a hematopoetic stem cell (HSC) mobilization agent. When Burixafor hydrobromide is given intravenously (IV) alone at a dose of 3.14 mg/kg it has been shown to result in a 7.8 fold mean increase in peripheral blood CD34+ (a HSC marker) cells 6-hours post-infusion.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Maryland
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Baltimore, Maryland, États-Unis, 21287
- Johns Hopkins University
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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:
- Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study
- Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
- Male aged 18 years and above
- Eastern cooperative group (ECOG) performance status ≤2
- Documented histologically confirmed adenocarcinoma of the prostate
- Metastatic prostate cancer to the bone as documented by positive bone scan imaging
- Patient must be eligible for chemotherapy with docetaxel
- Patient must have evidence of castrate resistant prostate cancer as evidenced by a confirmed rising PSA (per Prostate Cancer Working Group 2 [PCWG2] criteria) and a castrate serum testosterone level (i.e. ≤ 50 mg/dL).
Exclusion Criteria:
- Have known allergies, hypersensitivity, or intolerance to docetaxel or dexamethasone or their excipients
- Prior pelvic radiation (e.g. external beam, brachytherapy, etc) that, in the opinion of the investigator, may lead to decreased bone marrow cellularity in a marrow sample obtained from a pelvic bone marrow biopsy
Ongoing systemic therapy (other than a GnRH agonist/antagonist) for prostate cancer including, but not limited to:
- CYP-17 inhibitors (e.g. ketoconazole, abiraterone)
- Antiandrogens (e.g. bicalutamide, nilutamide)
- Second generation antiandrogens (e.g. enzalutamide)
- Immunotherapy (e.g. sipuleucel-T, ipilimumab)
- Chemotherapy (e.g. docetaxel, cabazitaxel)
- Prior radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153, etc) within the past year
- Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
- Active infection or other medical condition that would make corticosteroids (i.e. dexamethasone) use contraindicated
- Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg) Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
- Severe hepatic impairment (Child-Pugh Class C)
- History of pituitary or adrenal dysfunction (note: the use of daily steroids does not exclude someone from participating in this study)
- Have poorly controlled diabetes (HgB A1C ≥ 8%)
- Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur actif: burixafor hydrobromide
Four daily doses of burixafor hydrobromide alone
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Investigators will determine the kinetics of PCa cell release into the blood with four daily dosages of Burixafor hydrobromide alone or in combination with G-CSF
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|
Comparateur actif: G-CSF
G-CSF will be given as a daily subcutaneous (SC) injection beginning 4 days prior to Burixafor hydrobromide and continuing through the 4 days of Burixafor hydrobromide treatment
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G-CSF will be given as a daily subcutaneous (SC) injection beginning 4 days prior to Burixafor hydrobromide and continuing through the 4 days of Burixafor hydrobromide treatment
Autres noms:
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Expérimental: Docetaxel
Investigators will administer a single 75 mg/m2 IV dose of docetaxel. Twenty-one days later investigators will re-treat enrolled men with the optimal mobilization strategy + docetaxel IV. The second dose of docetaxel being given in combination with the optimal mobilization strategy will be chosen according to a standard 3+3 dose escalation schema, in which the dose of bruixafor +/- G-CSF will be held constant and the dose of docetaxel will escalate between three dose-levels: 1) docetaxel 30 mg/m2 IV, 2) docetaxel 60 mg/m2 IV, and 3) docetaxel 75 mg/m2 |
Investigators will administer a single 75 mg/m2 IV dose of docetaxel.
Twenty-one days later investigators will re-treat enrolled men with the optimal mobilization strategy + docetaxel IV.
The second dose of docetaxel being given in combination with the optimal mobilization strategy will be chosen according to a standard 3+3 dose escalation schema, in which the dose of bruixafor +/- G-CSF will be held constant and the dose of docetaxel will escalate between three dose-levels: 1) docetaxel 30 mg/m2 IV, 2) docetaxel 60 mg/m2 IV, and 3) docetaxel 75 mg/m2
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Mobilization of DTCs from bone marrow
Délai: 2 years
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Measure the number of CTCs in the peripheral blood.
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2 years
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time
Délai: 2 years
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This will be reported as number of tumor cells/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.
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2 years
|
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Kinetics of hematopoietic stem cell (HSC) mobilization by quantifying the number of circulating HSCs per milliliter of blood over time
Délai: 2 years
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This will be reported as number of HSC/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.
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2 years
|
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PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel
Délai: 2 years
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2 years
|
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Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel
Délai: 2 years
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Safety will be evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events
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2 years
|
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Exploratory biomarker Assessment on CTCs/DTCs
Délai: 2 years
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Examples of these may include, but are not limited to: assessment of cell cycle kinetics, apoptosis, PTEN status, MYC alterations, whole genome, whole exome, and transcriptome analysis
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2 years
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Collaborateurs et enquêteurs
Les enquêteurs
- Chercheur principal: Kenneth Pienta, MD, Johns Hopkins University
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
- Tumeurs
- Tumeurs urogénitales
- Tumeurs par site
- Tumeurs génitales, homme
- Maladies de la prostate
- Tumeurs prostatiques
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents antinéoplasiques
- Facteurs immunologiques
- Modulateurs de tubuline
- Agents antimitotiques
- Modulateurs de mitose
- Adjuvants, immunologique
- Docétaxel
- Lénograstim
Autres numéros d'identification d'étude
- J14177
- IRB00054180 (Autre identifiant: JHM IRB)
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