Prostate CancerPhase 1NCT02478125
Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
A Phase 1 study testing Burixafor Hydrobromide, Docetaxel and G-CSF in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Burixafor Hydrobromide, Docetaxel and G-CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to May 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
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. 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.
Read the detailed description
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.
- Conditions
- Prostate Cancer
- Keywords
- metastatic castrate resistant prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Burixafor HydrobromideDrug
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
DocetaxelDrug
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
G-CSFDrug
Also called granulocyte-colony stimulating factor
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
| Study group | Role | What they receive |
|---|---|---|
| burixafor hydrobromide | Active comparator | Four daily doses of burixafor hydrobromide alone Receives: Drug: Burixafor Hydrobromide |
| G-CSF | Active comparator | 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 Receives: Drug: G-CSF |
| Docetaxel | Experimental | 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 Receives: Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mobilization of DTCs from bone marrow
Measure the number of CTCs in the peripheral blood.
Measured: 2 years
Secondary outcomes (5)
Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time
This will be reported as number of tumor cells/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.
Measured: 2 years
Kinetics of hematopoietic stem cell (HSC) mobilization by quantifying the number of circulating HSCs per milliliter of blood over time
This will be reported as number of HSC/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.
Measured: 2 years
PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel
Measured: 2 years
Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel
Safety will be evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events
Measured: 2 years
Exploratory biomarker Assessment on CTCs/DTCs
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2015 (estimated)
- Study startJul 2016
- Primary completionMay 2017
- Study completionMay 2017
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Prostate Cancer Foundation, TaiGen Biotechnology Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Kenneth Pienta, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02478125
- Sponsor's protocol ID
- J14177
- Other IDs
- IRB00054180
- Status last verified
- Jan 2019
- First submitted
- 10 Jun 2015
- Last updated
- 18 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT02478125
- Acronym / sponsor ID
- J14177
- Conditions
- Prostate Cancer
- Keywords
- metastatic castrate resistant prostate cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Prostate Cancer Foundation, TaiGen Biotechnology Co., Ltd.
- Study start
- Jul 2016 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 23 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. 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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| burixafor hydrobromide | Active comparator | Drug: Burixafor HydrobromideFour daily doses of burixafor hydrobromide alone |
| G-CSF | Active comparator | Drug: G-CSFG-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 |
| Docetaxel | Experimental | Drug: DocetaxelInvestigators 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (16 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Burixafor HydrobromideInvestigators 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 | Drug | burixafor hydrobromide |
| DocetaxelInvestigators 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 | Drug | Docetaxel |
| G-CSFAlso: granulocyte-colony stimulating factorG-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 | Drug | G-CSF |
Primary outcome
Mobilization of DTCs from bone marrow
Time frame: 2 years
Measure the number of CTCs in the peripheral blood.
5 secondary outcomes
Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time
Time frame: 2 years
Kinetics of hematopoietic stem cell (HSC) mobilization by quantifying the number of circulating HSCs per milliliter of blood over time
Time frame: 2 years
PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel
Time frame: 2 years
Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel
Time frame: 2 years
Exploratory biomarker Assessment on CTCs/DTCs
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth Pienta, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Burixafor Hydrobromide, Docetaxel and G-CSF in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mobilization of DTCs from bone marrow (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2019.