A Phase 0 Trial of (111)Indium CHX-A DTPA Trastuzumab Imaging in Cancer
- Trastuzumab (Herceptin(Trademark)), targets HER2 (aka: neu, ErbB2, c-erb-B2) on the
surface of cancer cells and is used in the treatment of breast cancers that overexpress
HER2/Neu (Erb2). It has also been demonstrated that other malignancies express HER2/Neu
- Radiolabeling trastuzumab could allow human biodistribution studies, noninvasive
assessment of HER2/Neu (Erb2) expression, identification of HER2/Neu (Erb2) positive
metastases, monitoring of treatment response and establishment of dosimetry for future
- We have developed a chelated form of trastuzumab, CHX-A DTPA-trastuzumab, that can
bind a number of radioisotopes including (111)In, (212), (213)Bi, (212)Pb (86), (90)Y
and (177)Lu which have alpha, beta and gamma emissions for imaging and therapy.
- We believe that the agent will be safe based on the low dose of trastuzumab (up to a
maximum of 200 mcg of protein or less than1% of the typical loading dose of trastuzumab
in a 70 Kg human) and the low dose of radioactivity (5mCi).
- Whereas trastuzumab therapy is generally only useful in tumors that highly express
HER2/Neu (Erb2), (111)In-CHX-A DTPA trastuzumab (henceforth (111)Indium-trastuzumab )
will image tumors that are not only highly expressing HER2/Neu (Erb2) but also tumors
that are poorly expressing HER2/Neu (Erb2) as documented by preclinical data.
- The primary objective is to compare uptake of 111Indium trastuzumab with HER2/Neu
(Erb2) status of the tumor as determined by IHC
- Secondary objectives will be to establish safety of (111)Indium trastuzumab, determine
the optimal timing of imaging as a function of HER2/Neu (Erb2) status, and determine
biodistribution of the agent in normal organs and pharmacokinetics of serum clearance.
- Participants with a history of primary or metastatic cancer (other than melanoma, basal
cell carcinoma, sarcoma or lymphoma) with known solid tumor size greater than or equal
to 1.5 cm.
- Availability of HER2/Neu (Erb2) expression by immunohistochemistry (IHC) or pathology
or biopsy specimen can be provided on which such an analysis can be made.
- The design of this pilot trial follows the concept of a Phase 0 or Exploratory IND
- Participants with known malignancy greater than or equal to 1.5cm and known
HER2/Neu(ErbB2) tumor status (0, 1+, 2+ or 3+) by IHC or FISH.
- After receiving 5 mCi of (111)Indium-trastuzumab, all participants will undergo gamma
camera scans at approximately 24-72 hours after injection. In some subjects, an
additional imaging session may be required 24 hours after the first set of images as
physiologic bowel clearance is variable and may obscure the lesion of interest on the
- We will accrue 20 participants to this study.
- A total of 8 blood samples (4 lab tests and up to 4 for pharmacokinetics) will be
obtained from each participant to establish toxicity and the pharmacokinetics of
- Images will be correlated with IHC status using tumor to background ratios and the
optimal scanning strategy with regard to HER2/neu(ErbB2) expression will be determined.
- Participants who undergo a therapy thought to target or effect HER2 will have the
option of undergoing repeat imaging following therapy.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Correlation of uptake with HER2/neu status of tumor.
Peter L Choyke, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|