Imaging CXCR4 Expression in Subjects With Cancer Using 64 Cu-Plerixafor
Status:
Terminated
Trial end date:
2018-07-10
Target enrollment:
Participant gender:
Summary
In mouse models and in patients, expression of the chemokine receptor CXCR4 on various
cancers has been correlated with aggressive biological behavior, including increased rates
and certain sites of metastasis, and decreased survival. Plerixafor (Mozobil ; Genzyme;
Cambridge, MA) has been identified as a specific inhibitor of CXCR4, and it is currently
approved by the Food and Drug Administration as a stem-cell mobilizing agent in combination
with granulocyte colony-stimulating factor in the treatment of non-Hodgkin's lymphoma and
multiple myeloma. Our group has recently shown that plerixafor can be labeled with the
positron-emitting radionuclide copper-64((64)Cu) to form (64)Cu-plerixafor, which can be used
to visualize CXCR4-positive tumor xenografts in mice using small-animal positron emission
tomography (PET). Determining CXCR4 expression in tumors using (64)Cu-plerixafor and
PET/computerized tomography (CT) scanning could be useful in predicting tumor behavior and
responses to current and experimental therapies, including therapies targeting CXCR4, which
could lead to more effective personalized cancer treatments.
This study s primary objective is to evaluate (64)Cu-plerixafor as an imaging agent for
quantifying CXCR4 expression in subjects (greater than or equal to 18 years of age) with
cancer; at least 1 detectable solid tumor of greater than or equal to 2 cm in diameter found
outside of the lymph nodes, bone marrow, liver, gallbladder, kidney, bladder, and brain; and
preexisting biopsies of the tumors obtained since the first detection of the current
occurrence/recurrence of disease. The secondary objectives are to correlate (64)Cu-plerixafor
standardized uptake value in the target lesion with the level of CXCR4 expression detected
via immunohistochemistry and to calculate human dosimetry for (64)Cu-plerixafor.
Preexisting tumor biopsies from less than or equal to 75 subjects recruited from the National
Cancer Institute and the Georgetown University Hospital will be evaluated for CXCR4
expression via immunohistochemistry. Subjects who meet the eligibility criteria will continue
onto the study. Five subjects with CXCR4-positive tumor biopsies will be administered an
initial intravenous infusion of (64)Cu-plerixafor (8 +/-0.8 mCi ; 0.48+/- 0.048 rem; not to
exceed 5 microg of (64)Cu -plerixafor) over 2 minutes. They will then undergo an initial
low-dose transmission CT scan followed by 3 consecutive torso PET scans as soon as practical
after the infusion, and 2 additional PET/CT scans at 4 hours +/- 1 hour and 24 hours +/- 2
hours post-infusion. Human dosimetry will be calculated based on these results, and a maximum
dose will be used, not to exceed the calculated limit of a total effective dose of 5 rem, or
the radiation exposure limit for each organ. The remaining subjects with CXCR4-positive
(n=15) and CXCR4-negative (n=5) tumor biopsies will be administered 64Cu-plerixafor at the
same, or a newly calculated dose, and will undergo 1 PET/CT scan between 1 and 4 hours
post-infusion, depending on the dosimetry results. All subjects will undergo one
comprehensive final study visit between study days 19 and 23 (11-17 days after injection with
(64)Cu -plerixafor). Additionally, blood will be collected 2 more times between study days
13-16 and study days 26-30 to measure blood cell counts.
...
Phase:
Early Phase 1
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)