- ICH GCP
- Registr klinických studií v USA
- Klinická studie 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
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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Maryland
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Baltimore, Maryland, Spojené státy, 21287
- Johns Hopkins University
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Aktivní komparátor: 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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Aktivní komparátor: 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
Ostatní jména:
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Experimentální: 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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Mobilization of DTCs from bone marrow
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time
Časové okno: 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
Časové okno: 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
Časové okno: 2 years
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2 years
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Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel
Časové okno: 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
Časové okno: 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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Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Kenneth Pienta, MD, Johns Hopkins University
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Novotvary
- Urogenitální novotvary
- Novotvary podle místa
- Genitální novotvary, muži
- Onemocnění prostaty
- Novotvary prostaty
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Antineoplastická činidla
- Imunologické faktory
- Tubulinové modulátory
- Antimitotické látky
- Modulátory mitózy
- Adjuvans, Imunologická
- Docetaxel
- Lenograstim
Další identifikační čísla studie
- J14177
- IRB00054180 (Jiný identifikátor: JHM IRB)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
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