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

NCT02478125 | Terminated Phase 1 DMC

• 2 other identifiers: J14177IRB00054180
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

metastatic castrate resistant prostate cancer

Outcome Measures

Primary Outcomes (1)

• Mobilization of DTCs from bone marrow

  Measure the number of CTCs in the peripheral blood.

  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

  2 years

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

  2 years

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

  2 years

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

  2 years

• Exploratory biomarker Assessment on CTCs/DTCs

  2 years

Study Arms (3)

burixafor hydrobromide

ACTIVE COMPARATOR

Four daily doses of burixafor hydrobromide alone

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

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

Drug: Docetaxel

Interventions

Burixafor Hydrobromide DRUG

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

burixafor hydrobromide

Docetaxel DRUG

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

Docetaxel

G-CSF DRUG

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

Also known as: granulocyte-colony stimulating factor

G-CSF

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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%)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Prostate Cancer Foundation: collaborator
• TaiGen Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Kenneth Pienta, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 23, 2015
• Study Start: July 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: January 18, 2019

Record last verified: 2019-01

Locations

US (1)