Breast Cancer
Conditions
Keywords
MRI, pHLIP® ICG, Imaging, Tumor stage T1-T2, 21-225, SPY-PHI Systems
Brief summary
The purpose of this study is to find out whether pre-operative mpMRI using additional MRI sequences may improve surgical outcomes by providing more accurate information about the extent and acidity of the tumor than standard MRI, and to see whether the use of the fluorescent imaging agent pHLIP ICG and NIRF imaging during surgery is a safe approach that may allow the surgeon to see the tumor and nearby tissues that contain cancer cells more clearly and remove them completely. During the Phase IIa part of this study, the safe dose of pHLIP ICG will be used that makes it easy for the surgeon to see the tumor and the nearby tissues and structures that may contain cancer cells. This study is the first to test pHLIP ICG in people, and the first to test the use of pHLIP ICG with mpMRI and NIRF imaging in surgery for breast cancer.
Detailed description
his protocol involves performing first-in-human imaging with pHLIP® ICG in consecutive patients with newly diagnosed primary BC (tumor stage T1-T2 with or without lymph node metastases) undergoing breast conserving treatment at MSK. All imaging will be obtained either at MRI staging before surgery and during definite surgical treatment; no additional invasive procedures will be necessary. The information collected in the phase I part of this study will not be used for diagnostic purposes, and neither will the information be used to assess the patients' response to therapy nor adjust the clinical management of the patient. During phase IIa of the study, if pHLIP® ICG NIRF imaging indicates tumor in areas outside of the planned resection area, biopsy samples will be taken from these areas and submitted for pathological analysis. A standard 3+3 followed by dose expansion clinical design plus 3 patients with selected dose (the minimum number of patients is 2, the maximum number of patients is 27, and the expected number of patients is 15 assuming 3 patients per 4 dose levels and 3 additional patients with the selected dose) will be used.
Interventions
DIAGNOSTIC_TESTpHLIP® ICG NIRF imaging
Pre-operative research MRI will be performed 1-3 weeks prior to the surgery. single pHLIP® ICG injection will be administered i.v. by a radiologist on the protocol one day prior to scheduled surgery on the occasion of presurgical localization (12-36 hours prior to the surgery). In Phase I, we propose to investigate 4 different doses: Dose level 1 = 0.04 mg/kg Dose level 2 = 0.075 mg/kg Dose level 3 = 0.15 mg/kg Dose level 4 = 0.30 mg/kg In Phase IIa, the researchers propose to administer selected in Phase I dose of pHLIP® ICG. In Phase IIa, the researchers propose to administer pHLIP® ICG at DL2, DL3 or DL4 at different time points prior to surgery ranging from 12-110 hours, with targeted enrollment of 12 patients. Next, the selected optimal dose and timing will be used with targeted enrollment of 28 patients. The total number of subjects in Phase IIa study is 40.
Sponsors
Memorial Sloan Kettering Cancer Center
Stryker Instruments
pHLIP Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or greater * Biopsy proven primary breast malignancy (BI-RADS 6) * Tumor stage Tis, T1 and T2, lesion size \> 1 cm * Primary surgical treatment with breast conservation * No previous treatment * ECOG performance of 0-2
Exclusion criteria
* Life expectancy \< 3 months * Pregnancy or lactation * Known metastatic liver disease, hepatic neoplasms (benign and malignant), biliary atresia, chronic liver disease (CLD) and cirrhosis. * Known moderate hepatic impairment (in phase I, and in phase IIa dependent on safety profile established in phase I) * Known hypersensitivity to indocyanine green. * Individuals with impaired-decision making capacity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | 15 days post pHLIP® ICG injection | is defined as a clinically significant adverse event recorded within 3 hours after pHLIP® ICG administration or an abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, surgery, or concomitant medications, and meets the NCI common terminology criteria that are CTCAE Grade 3 or 4. |
| Concordance between the absence of optical signal and histopathological confirmation of absence of malignancy. (Phase II) | 1 year | Each lesion will be classified as positive or negative based on imaging and compared against histopathology as the gold standard. |
| Visualization of a lesion with pHLIP® ICG (Phase II) | up to 6 months | The visualization of a lesion with pHLIP® ICG NIRF (Likert score is ≥1) will be considered positive for malignancy. No visualization of a lesion or visualization at the background level (Likert score is 0) with pHLIP® ICG NIRF will be considered negative for malignancy. |
Countries
United States
Contacts
CONTACTGiacomo Montagna, MD
CONTACTMonica Morrow, MD
PRINCIPAL_INVESTIGATORGiacomo Montagna, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed