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

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.

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.