Targeted Silica Nanoparticles in Imaging Sentinel Lymph Nodes in Patients with Newly-Diagnosed and / or Recurrent Melanoma, Breast, Oral Cavity Squamous Cell, or Colorectal Cancer

This pilot phase I / II trial studies how well targeted silica nanoparticles work in imaging lymph nodes in patients with melanoma, breast, oral cavity squamous cell, or colorectal cancer that has come back (recurrent) and / or is newly-diagnosed. During surgery, it can be difficult to visualize nodes with cancer called sentinel lymph nodes. Targeted silica nanoparticles can be used to detect disease that has spread to local / regional nodes and allow the surgeon to remove the sentinel lymph nodes without harming normal lymph nodes.

Inclusion Criteria

• Histologically confirmed diagnosis of melanoma, breast cancer, or colorectal cancer, at Memorial Sloan-Kettering Cancer Center (MSKCC)
• Have one of the following disease histories: * Newly-diagnosed or recurrent (local, regional, metastatic) malignant melanoma, oral cavity squamous cell carcinoma, or breast cancer patients in whom sentinel lymph node (SLN) mapping is indicated ** Residual clinically or radiographically evident tumor, including primary cutaneous and mucosal melanomas ** Prior radiation therapy, chemotherapy, or surgery in patients requiring flap reconstruction in the head and neck region ** Newly-diagnosed patients with previous excisional biopsy OR ** Newly-diagnosed colorectal cancer patients in whom SLN mapping and total mesorectal excision with lateral pelvic sidewall dissection is indicated
• At the discretion of the physician or surgeon, normal baseline cardiac function based upon pre-operative evaluation
• At the discretion of the physician or surgeon, absolute neutrophil count (ANC) > 1000/mcl
• At the discretion of the physician or surgeon, platelets > 100,000/mcl
• At the discretion of the physician or surgeon, bilirubin level of < 2.0 mg/dl in the absence of a history of Gilbert's disease (or pattern consistent with Gilbert’s)
• For melanoma patients, if patients have a history of malignancy other than melanoma and other skin cancers in the past five years, their inclusion is up to the discretion of the physician
• All patients of childbearing and child-creating age must be using an acceptable form of birth control
• Women who are pre-menopausal must have a negative serum pregnancy test

Exclusion Criteria

• Known pregnancy or breast-feeding
• Medical illness unrelated to the tumor which in the opinion of the attending physician and principal investigator will preclude administration of the agent; this includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association classification III or IV heart disease

PRIMARY OBJECTIVES:

I. Assess whether locally injected non-radioactive fluorescent cRGDY-PEG-Cy5.5 C dots (cRGDY PEG-Cy5.5 C dots) injected about the primary tumor site or within the mucosa (for colorectal cases) can identify fluorescent nodes within the nodal basin of colorectal malignancies intraoperatively or ex vivo following axillary dissection in breast cancer patients to determine the true positive and false positive rates for cancer detection, as determined by pathological examination. (Phase I)

II. Determine the proportion of lymph nodes identified by 99mTc sulfur colloid that are positive by cRGDY-PEG-Cy5.5-C dot visualization. (Phase II)

III. Determine the proportion of patients in whom the surgical approach or extent of dissection was altered as a result of cRGDY-PEG-Cy5.5C dot visualization. (Phase II)

IV. Determine whether the signal foci visualized optically correspond to lymph nodes or lymphatic channels. (Phase II)

V. Monitor for adverse reactions to the non-radioactive particle probe as a safety endpoint. (Phase II)

SECONDARY OBJECTIVES:

I. Determine whether a near infrared (NIR) fluorescence signal-to-background ratio (SBR) of 1.1 or greater optimizes image contrast and enables identification of diseased nodes, along with the smallest dose of cRGDY-PEG-Cy5.5-C dots needed to achieve this threshold ratio. (Phase I)

II. Compare detection rates of cRGDY-PEG-Cy5.5-C dots and Tc99m sulfur colloid for pathology-positive sentinel lymph nodes (SLNs). (Phase II)

III. Correlate optical signal with tumor burden assessments. (Phase II)

IV. Assess alpha-v integrin expression levels in primary and nodal tissue specimens derived from a subset of patients. (Phase II)

OUTLINE:

Up to 24 hours before or during surgery, patients receive fluorescent cRGDY PEG-Cy5.5 C dots intradermally (ID) or via intramucosal or periareolar injections.

After completion of study, patients are followed up at 2 weeks.

Trial Phase Phase I/II

Trial Type Diagnostic

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Hilda E Stambuk

• Primary ID 13-249
• Secondary IDs NCI-2016-01052
• Clinicaltrials.gov ID NCT02106598