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

NCT ID: NCT02478125

Last Updated: 2019-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2017-05-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

burixafor hydrobromide

Four daily doses of burixafor hydrobromide alone

Group Type: ACTIVE_COMPARATOR

Burixafor Hydrobromide

Intervention Type: 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

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

Group Type: ACTIVE_COMPARATOR

G-CSF

Intervention Type: 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

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

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: 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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

granulocyte-colony stimulating factor

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Prostate Cancer Foundation

OTHER

Sponsor Role: collaborator

TaiGen Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kenneth Pienta, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

IRB00054180

Identifier Type: OTHER

Identifier Source: secondary_id

J14177

Identifier Type: -

Identifier Source: org_study_id