A Phase 0 Trial of (111)Indium CHX-A DTPA Trastuzumab Imaging in Cancer
18 Years
N/A
Female
Breast Cancer
Trial Information
A Phase 0 Trial of (111)Indium CHX-A DTPA Trastuzumab Imaging in Cancer
Background:
- 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
(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.
Objectives:
- 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.
Eligibility:
- 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.
Design:
- 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.
Inclusion Criteria
- INCLUSION CRITERIA:
Participant must have histological confirmation of primary or metastatic cancer other than
melanoma, basal cell carcinoma, sarcoma, or lymphoma.
- Primary tumor or metastatic focus must be 1.5cm or greater in diameter as established
by palpation, ultrasound, mammography, CT or MRI.
- Participant must be 18 years or older.
- Availability of tumor tissue (either from the initial primary tumor or from current
tumor lesion) for performing IHC or FISH analysis for HER2/Neu (Erb2)
- Chemistry and CBC parameters: serum creatinine less than or equal to 1.4mg/dl. SGOT
and SGPT less than or equal to 2 times of the upper limits of normal; total
bilirubin, of less than or equal to 2 times the upper limits of normal or 3.0 mg/dl
in patients with Gilbert's syndrome; platelet count must be greater than 100,00.
- ECOG Performance score of 0 or 1.
- Ability to provide informed consent.
- Negative serum pregnancy test (within 48 hours of imaging agent injection) in women
of child bearing age and willingness to use contraception (barrier, abstinence,
non-hormonal) for 3 weeks after injection of (111)Indium trastuzumab if participant
is of child bearing age.
EXCLUSION CRITERIA:
- Known allergy to trastuzumab.
- Pregnant or lactating women.
- Participants for whom enrollment would significantly delay (greater than 2 weeks) the
scheduled standard of care therapy.
- Participants with an active second malignancy (excluding treated basal cell skin
carcinoma).
- History of cardiac disease (myocardial infarction, arrhythmias requiring therapy,
symptomatic valvular disease, cardiomyopathy, or pericarditis).
- Participants with any coexisting medical or psychiatric condition that is likely to
interfere with study procedures and/or results.
- Participants with severe claustrophobia.
- A participant who needs a nuclear medicine scan other than a PET scan as part of
their work-up cannot enroll until these scans have been completed.
- Gamma-camera table restrictions preclude scanning participants greater than 350 lbs
(160 Kg)
- With the exception of AT13387 and PU-H71, and Ad5f35HER2ECTM transduced autologous
dendritic cell vaccine participants cannot have received another experimental drug
within 14 days prior to or during study enrollment.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Outcome Measure:
Correlation of uptake with HER2/neu status of tumor.
Safety Issue:
No
Principal Investigator
Peter L Choyke, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
070101
NCT ID:
NCT01445054
Start Date:
February 2007
Completion Date:
Related Keywords:
- Breast Cancer
- Exploratory IND
- Gamma Camera
- SPECT Imaging
- Radionuclide
- Antibody Imaging
- 111 Indium Trastuzumab Imaging
- PET
- Breast Cancer
- Breast Neoplasms
Name | Location |
|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |
