Clinical trial NCT02478125: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: metastatic castrate resistant prostate cancer
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Prostate Cancer Foundation
name: TaiGen Biotechnology Co., Ltd.
First posted: 2015-06-23
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mobilization of DTCs from bone marrow
timeFrame: 2 years
Secondary outcomes:
measure: Kinetics of disseminated tumor cell mobilization by quantifying the number of circulating tumor cells per milliliter of blood over time
timeFrame: 2 years
measure: Kinetics of hematopoietic stem cell (HSC) mobilization by quantifying the number of circulating HSCs per milliliter of blood over time
timeFrame: 2 years
measure: PSA response to treatment with Burixafor hydrobromide alone and Burixafor hydrobromide and docetaxel
timeFrame: 2 years
measure: Safety of Burixafor hydrobromide +/- GCSF +/- docetaxel
timeFrame: 2 years
measure: Exploratory biomarker Assessment on CTCs/DTCs
timeFrame: 2 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Kenneth Pienta, MD
role: PRINCIPAL_INVESTIGATOR
References: