111 Indium CHX-A DTPA Trastuzumab (Indium-Herceptin) for Imaging Breast Cancer
- Some breast cancer cells have specific proteins (receptors) on their surface that make the tumor grow faster than normal cells. One of these receptors is called HER2/neu.
- An FDA-approved drug called Herceptin attaches to HER2/neu if it is present on the cancer cell.
- Indium-Herceptin is an agent in which a tiny amount of radioactivity called Indium has been attached to a tiny amount of Herceptin.
-To see if Indium-Herceptin provides information about the characteristics of the breast cancer in women whose tumors express HER2/neu and those whose tumors do not.
-Women 18 years or older with primary or metastatic breast cancer who have not received treatment with herceptin for at least 6 months before enrollment into the study.
- Tissue from the patient s original breast or tumor biopsy is analyzed for HER2/neu status.
- Patients have a physical examination and review of medical records.
- Patients receive an injection of Indium-Herceptin, followed by scanning with a gamma camera that detects the radioactivity in the Indium-Herceptin.
- Patients return to the clinic 1, 2, 3 and 7 days later for repeat imaging to determine the best time to image after injection of Indium-Herceptin.
- Blood samples are obtained every day of scanning to monitor the effects, if any, of the Indium-Herceptin and to see how fast the agent leaves the body.
Drug: 111Indium CHX-A DTPA trastuzumab
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||A Phase 0 Trial of (111)Indium CHX-A DTPA Trastuzumab Imaging in Cancer|
- Uptake of 111Indium-CHX-A DTPA trastuzumab as determined by IHC [ Time Frame: Within 5 days after enrollment ] [ Designated as safety issue: No ]
- Establish safety of 111Indium-trastuzumab. [ Time Frame: within 5 days after enrollment ] [ Designated as safety issue: Yes ]
- Determine optimal timing of 111Indium-CHX-A DTPA trastuzumab imaging as a function of HER2/ Neu(ErbB2) status. [ Time Frame: completion of study ] [ Designated as safety issue: No ]
- Determine the biodistribution of the agent in normal organs [ Time Frame: completion of study ] [ Designated as safety issue: No ]
- Determine the pharmacokinetic serum clearance of 111Indium- CHX-A DTPA trastuzumab [ Time Frame: completion of study ] [ Designated as safety issue: No ]
- To evaluate the change in 111Indium-CHX-A DTPA trastuzumab uptake in tumors following treatment with a HER2 targeted therapy [ Time Frame: completion of study ] [ Designated as safety issue: No ]
|Study Start Date:||February 2007|
|Study Completion Date:||August 2014|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Participants with known malignancy 1.5cm and known HER2/Neu(ErbB2) tumor status (0, 1+, 2+ or 3+) byeither IHC or FISH.
Drug: 111Indium CHX-A DTPA trastuzumab
The 111Indium-trastuzumab will be administered in the Clinical Center, Nuclear Medicine Department intravenously over a 10-15 minute period using an intravenous catheter
- Trastuzumab (Herceptin ), 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 (Erb2).
- 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 radioimmunotherapy.
- 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 (xIND) study.
- 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 initial scan.
- 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 clearance.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01445054
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Peter L Choyke, M.D.||National Cancer Institute (NCI)|