Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02478125
Recruitment Status : Terminated (Low accrual)
First Posted : June 23, 2015
Last Update Posted : January 18, 2019
Sponsor:
Collaborators:
Prostate Cancer Foundation
TaiGen Biotechnology Co., Ltd.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Burixafor Hydrobromide Drug: Docetaxel Drug: G-CSF Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer
Actual Study Start Date : July 2016
Actual Primary Completion Date : May 2017
Actual Study Completion Date : May 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Docetaxel

Arm Intervention/treatment
Active Comparator: burixafor hydrobromide
Four daily doses of burixafor hydrobromide alone
Drug: Burixafor Hydrobromide
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

Active Comparator: 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
Drug: 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
Other Name: granulocyte-colony stimulating factor

Experimental: 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

Drug: 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




Primary Outcome Measures :
  1. Mobilization of DTCs from bone marrow [ Time Frame: 2 years ]
    Measure the number of CTCs in the peripheral blood.


Secondary Outcome Measures :
  1. Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time [ Time Frame: 2 years ]
    This will be reported as number of tumor cells/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.

  2. Kinetics of hematopoietic stem cell (HSC) mobilization by quantifying the number of circulating HSCs per milliliter of blood over time [ Time Frame: 2 years ]
    This will be reported as number of HSC/mL at multiple time points following infusion of Burixafor hydrobromide with and without G-CSF.

  3. PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel [ Time Frame: 2 years ]
  4. Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel [ Time Frame: 2 years ]
    Safety will be evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events

  5. Exploratory biomarker Assessment on CTCs/DTCs [ Time Frame: 2 years ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
  3. Male aged 18 years and above
  4. Eastern cooperative group (ECOG) performance status ≤2
  5. Documented histologically confirmed adenocarcinoma of the prostate
  6. Metastatic prostate cancer to the bone as documented by positive bone scan imaging
  7. Patient must be eligible for chemotherapy with docetaxel
  8. 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:

  1. Have known allergies, hypersensitivity, or intolerance to docetaxel or dexamethasone or their excipients
  2. 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
  3. 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)
  4. Prior radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153, etc) within the past year
  5. 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
  6. Active infection or other medical condition that would make corticosteroids (i.e. dexamethasone) use contraindicated
  7. 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
  8. Severe hepatic impairment (Child-Pugh Class C)
  9. History of pituitary or adrenal dysfunction (note: the use of daily steroids does not exclude someone from participating in this study)
  10. Have poorly controlled diabetes (HgB A1C ≥ 8%)
  11. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02478125


Locations
Layout table for location information
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Prostate Cancer Foundation
TaiGen Biotechnology Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Kenneth Pienta, MD Johns Hopkins University
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02478125    
Other Study ID Numbers: J14177
IRB00054180 ( Other Identifier: JHM IRB )
First Posted: June 23, 2015    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: January 2019
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
metastatic castrate resistant prostate cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Docetaxel
Sargramostim
Lenograstim
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic