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Background: Combined use of a radiocolloid and a vital blue dye is recommended for accurate lymphatic mapping and sentinel lymph node (SLN) identification in breast cancer. However, vital blue dyes can cause tattooing, skin necrosis and severe allergic reactions. Moreover, the vital blue dyes are only able to detect 70% or less of SLNs in large multi-center trials. Hence, there is an unmet need to develop new lymphatic mapping agents that could potentially replace vital blue dyes. We have previously, in a Phase I trial, reported on the safety of VST-1001 (dilute fluorescein) in SLN identification. Here we report the Phase II data of VST-1001 and direct visualization devices in lymphatic mapping, SLN identification, and safety in clinically node negative breast cancer. Methods: This prospective Phase II, multi-center, non-randomized, single-arm, open-label, single-dose clinical trial enrolled patients (pts) with DCIS and clinical stage I/II breast cancer eligible for SLN biopsy. All pts had SLN localization with technetium-99m-sulfur colloid (Tc99mSC) and intraoperative lymphatic mapping with 0.1% VST-1001 injected peritumorally, periareolarly, and/or intradermally. SLN radioactivity was identified with a gamma probe, and VST-1001 fluorescence was induced by light emitting diodes and detected as yellowish-green fluorescence in the visible light range with notch filter spectacles. The primary endpoint was the ability of VST-1001 to localize lymph nodes. SLN concordance of Tc99mSC radioactivity and VST-1001 fluorescence, and safety were also assessed. Results: Eighty-seven women and 2 men with a median age of 60 yrs (range, 37-77) were enrolled. Primary tumor T-stage was: 12.4% T0, 62.9% T1, 23.6% T2, and 1.1% T3. Of the 89 pts, 87 (97.8%) had at least 1 radioactive SLN, and 86 (96.6%) at least 1 fluorescent SLN. Of a total of 198 SLN identified (mean 2.2 SLN/pt), 74.2% were fluorescent and radioactive, 11.6% were radioactive only, 8.6% were fluorescent only, and 5.1% were not radioactive or fluorescent. 82.8% of all SLNs were fluorescent. Twelve (13.5%) pts had microscopic metastatic breast cancer in 14 (7.1%) SLNs. Of the 14 SLNs with metastasis, 12 (85.7%) were both radioactive and fluorescent, 1 (7.1%) fluorescent only and 1 (7.1%) not radioactive or fluorescent and only suspicious on palpation. The fluorescent only SLN was identified in a patient with only 1 SLN and without VST-1001 the metastasis would have been missed. The only adverse event related to VST-1001 was intraoperative grade 2 allergic reaction of the ipsilateral breast in one pt. Intravenous anti-histamines were administered and the erythema resolved. Conclusions: VST-1001 safely localized lymph nodes in breast cancer. VST-1001 was able to localize lymph nodes that were not radioactive and had a high co-localization concordance with Tc99mSC. VST-1001 also appears to have a higher rate of SLN localization compared to that historically reported for vital blue dyes. In light of these data, VST-1001 may be an alternative SLN localizing agent to be used in conjunction with Tc99mSC in breast cancer pts, eliminating many of adverse events observed when using vital blue dyes without compromising SLN identification. Citation Format: Ross MI, Black DM, Mittendorf EA, Porretta JM, Bedrosian I, Caudle AS, Hwang RF, Meric-Bernstam F, Babiera GV, Brulotte M, Andtbacka RHI, Matsen CB. A phase II clinical trial of VST-1001 (dilute fluorescein) in lymphatic mapping and sentinel lymph node localization in clinically node negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-05.

Background: Combined use of a radiocolloid and a vital blue dye is recommended for accurate lymphatic mapping and sentinel lymph node (SLN) identification. However, vital blue dyes can cause tattooing, skin necrosis and allergic reactions. Hence, there is a great need for new lymphatic mapping agents. Here we describe the novel use of VST-1001 (dilute fluorescein) and direct visualization devices in lymphatic mapping and SLN identification. Methods: A prospective, non randomized, single arm, open label, single dose, dose-finding Phase I clinical trial in patients (pts) with high-grade DCIS and clinical stage I/II breast cancer eligible for SLN biopsy was performed. All pts had SLN localization with technetium-99m-sulfur colloid (Tc99mSC) and intraoperative lymphatic mapping with VST-1001 injected peritumorally, periareolarly, and/or intradermally. SLN radioactivity was identified with a gamma probe, and VST-1001 fluorescence was induced by light emitting diodes and detected as a yellowish-green fluorescence in the visible light range with notch filter spectacles. The primary endpoints were safety, ability of VST 1001 to localize lymph nodes, and the optimal dose of VST-1001. SLN concordance of Tc99mSC radioactivity and VST-1001 fluorescence was also assessed. Results: Fifteen women with a median age of 60 yrs (range, 43-80) were enrolled. In cohort 1, 5 pts received 0.01% VST-1001. All patients had at least 1 SLN that was fluorescent and radioactive. A total of 22 SLNs were identified, many with faint fluorescence. Per protocol, the dose of VST-1001 was increased, and in cohort 2, 10 patients received 0.1% VST-1001. All 10 (100%) pts in cohort 2 had at least 1 SLN that was fluorescent and radioactive. Of a total of 24 SLNs identified, 20 (83%) were fluorescent and radioactive, 2 (8%) were radioactive only, and 2 (8%) were fluorescent only. Four SLNs in 3 patients contained micrometastatic breast cancer; all 4 SLNs were radioactive and fluorescent. There were no adverse events related to VST-1001. A Phase II clinical trial is currently accruing. Conclusions: VST-1001 safely localized lymph nodes in breast cancer. VST-1001 was able to localize lymph nodes that were not radioactive and had a high concordance with Tc99mSC. VST-1001 may be a novel alternative to vital blue dyes in lymphatic mapping and lymph node localization. Citation Format: Ross MI, Bedrosian I, Black DM, Mittendorf EA, Caudle AS, Babiera GV, Hwang RF, Meric-Bernstam F, Grissom CB, Brulotte M, Andtbacka RHI. A phase I clinical trial of VST-1001 (dilute fluorescein) in lymphatic mapping and sentinel lymph node localization in clinically node negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-09.

2088 Background: Treatment options are limited for recurrent glioblastoma (GBM). Verubulin is a microtubule destabilizer and vascular disrupting agent that achieves high brain concentration relativ...