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Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer

Primary Purpose

Prostate Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Burixafor Hydrobromide

Docetaxel

G-CSF

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring metastatic castrate resistant prostate cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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:
1. CYP-17 inhibitors (e.g. ketoconazole, abiraterone)
2. Antiandrogens (e.g. bicalutamide, nilutamide)
3. Second generation antiandrogens (e.g. enzalutamide)
4. Immunotherapy (e.g. sipuleucel-T, ipilimumab)
5. 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.

Sites / Locations

Johns Hopkins University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

burixafor hydrobromide

G-CSF

Docetaxel

Arm Description

Four daily doses of burixafor hydrobromide alone

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

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

Outcomes

Primary Outcome Measures

Mobilization of DTCs from bone marrow

Measure the number of CTCs in the peripheral blood.

Secondary Outcome Measures

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.

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.

PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel

Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel

Safety will be evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events

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

Full Information

NCT ID

NCT02478125

First Posted

June 10, 2015

Last Updated

January 16, 2019

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Prostate Cancer Foundation, TaiGen Biotechnology Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02478125

Brief Title

Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer

Official Title

A Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Terminated

Why Stopped

Low accrual

Study Start Date

July 2016 (Actual)

Primary Completion Date

May 2017 (Actual)

Study Completion Date

May 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Prostate Cancer Foundation, TaiGen Biotechnology Co., Ltd.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

metastatic castrate resistant prostate cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

burixafor hydrobromide

Arm Type

Active Comparator

Arm Description

Four daily doses of burixafor hydrobromide alone

Arm Title

G-CSF

Arm Type

Active Comparator

Arm Description

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

Arm Title

Docetaxel

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Burixafor Hydrobromide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

Intervention Type

Drug

Intervention Name(s)

G-CSF

Other Intervention Name(s)

granulocyte-colony stimulating factor

Intervention Description

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

Primary Outcome Measure Information:

Title

Mobilization of DTCs from bone marrow

Description

Measure the number of CTCs in the peripheral blood.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time

Description

This will be reported as number of tumor cells/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.

Time Frame

2 years

Title

Kinetics of hematopoietic stem cell (HSC) mobilization by quantifying the number of circulating HSCs per milliliter of blood over time

Description

This will be reported as number of HSC/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.

Time Frame

2 years

Title

PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel

Time Frame

2 years

Title

Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel

Description

Safety will be evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events

Time Frame

2 years

Title

Exploratory biomarker Assessment on CTCs/DTCs

Description

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

Time Frame

2 years

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kenneth Pienta, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins University

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer

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