Breast Cancer, Lymph Node Mapping, Sentinel Lymph Node Biopsy
Conditions
Brief summary
This is a prospective, open label, multicenter, non-inferiority within-patient study to determine the effectiveness of IC2000 (Indocyanine Green (ICG) for Injection) and the SPY Portable Handheld Imaging System (SPY-PHI) as an intraoperative fluorescence visualization tool, in the visual identification of lymphatic vessels and lymph nodes (LNs) during lymphatic mapping and sentinel lymph node biopsy (SLNB) procedures as confirmed by Technitium99m (Tc99m) and Gamma Probe.
Interventions
COMBINATION_PRODUCTIC2000 and SPY-PHI
Investigational treatment to assess the effectiveness of IC2000 (Indocyanine Green (ICG) for Injection) and the SPY Portable Handheld Imaging System (SPY-PHI) as an intraoperative fluorescence visualization tool, in the visual identification of lymphatic vessels and lymph nodes (LNs) during lymphatic mapping and sentinel lymph node biopsy (SLNB) procedures in early stage breast cancer
COMBINATION_PRODUCTTc-99m radioactive colloid and Gamma Probe
Comparator; standard of care for sentinel lymph node biopsy (SLNB) procedures in early stage breast cancer
Sponsors
Novadaq Technologies ULC, now a part of Stryker
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm, open label, within patient study
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be 18 years of age or older 2. Subjects with American Cancer Society Clinical Stage 0 Ductal Carcinoma in Situ (DCIS) (Stage 0, Tis, N0, M0), IA (T1\*, N0, M0), IB ((T0, N1mi, M0) or T1\*, N1mi, M0)) or Stage IIA (T0, N1\*\*M0, or T1, N1\*\*, M0 or T2, N0, M0)1 breast cancer undergoing surgery to remove tumor draining LNs. Where: * Tis = Ductal carcinoma in situ * T0 = No evidence of primary tumor * T1 = Tumor ≤ 20 mm in greatest diameter * T1\* = Includes T1mi * T2 = Tumor \>20 mm but ≤ 50 mm in greatest diameter * N0 = No regional lymph node metastasisq1' * N1 = Metastasis to movable ipsilateral level I, II axillary LNs * N1\*\* = T0 and T1 tumors with nodal micro-metastasis only are excluded from Stage IIA and are classified Stage IB. * mi = Micro-metastasis * M0 = Disease has not metastasized from Stage IIA and are classified Stage IB. * M0= No evidence of metastasis * mi= Micrometastasis 3. Subjects with clinically negative nodal status (N0) with or without neoadjuvant chemotherapy 4. Subjects with negative metastatic involvement (M0) 5. Subjects of child-bearing potential must not be pregnant or lactating and must have a negative pregnancy test at Baseline 6. Have signed an approved informed consent form for the study 7. Be willing to comply with the protocol
Exclusion criteria
1. Have had prior axillary surgery or ipsilateral radiation in the breast(s) that is planned for the procedure 2. Advanced breast cancer subjects with stage IIB, III and IV 3. Known allergy or history of adverse reaction to ICG, iodine or iodine dyes 4. Subjects who have participated in another investigational study within 30 days prior to surgery 5. Pregnant or lactating subject 6. Subjects who, in the Investigator's opinion, have any medical condition that makes the subject a poor candidate for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Lymph Nodes Identified by IC2000/SPY-PHI Compared to the Proportion of Lymph Nodes Identified by Tc99m/Gamma Probe | From Technetium-99 (Tc-99m) injection to the completion of surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With at Least One Lymph Node Identified by IC2000/SPY-PHI, and the Proportion of Subjects With at Least One Lymph Node Identified by Tc99m/Gamma Probe | From Technetium-99 (Tc-99m) injection to the completion of surgery | — |
| Proportion of Lymph Nodes Identified by IC2000/SPY-PHI by Following a Fluorescent Lymphatic Vessel, and the Proportion of Identified Lymph Nodes With no Lymphatic Vessels Visible by IC2000/SPY-PHI | From Technetium-99 (Tc-99m) injection to the completion of surgery | — |
| To Assess the Safety of Intradermal Injection of IC2000 | From Technetium-99 (Tc-99m) injection to the completion of surgery | Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0 |
Countries
Canada, United States
Participant flow
Recruitment details
Subjects assessed for eligibility (n=153)
Participants by arm
| Arm | Count |
|---|---|
| IC2000/SPY-PHI Per standard of care, each subject will receive an injection of Tc-99m radioactive colloid. Then the periareolar area of the breast(s) identified with breast cancer will be injected (intradermal) twice with 0.05 ml of a 2.5 mg/ml solution of IC2000. Following the injection lymph node mapping will occur based on intraoperative fluorescence visualization using IC2000 and SPY-PHI. Lymph nodes will be excised following identification with IC2000 and SPY-PHI. The Gamma Probe will then be used with Tc-99m for confirmation of the excised lymph nodes as well as in the area of LN excision to ensure all LNs have been identified and excised.
IC2000 and SPY-PHI: Investigational treatment to assess the effectiveness of IC2000 (Indocyanine Green (ICG) for Injection) and the SPY Portable Handheld Imaging System (SPY-PHI) as an intraoperative fluorescence visualization tool, in the visual identification of lymphatic vessels and lymph nodes (LNs) during lymphatic mapping and sentinel lymph node biopsy (SLNB) procedures in early stage breast cancer
Tc-99m radioactive colloid and Gamma Probe: Comparator; standard of care for sentinel lymph node biopsy (SLNB) procedures in early stage breast cancer | 152 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | IC2000/SPY-PHI |
|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 11.5 |
| Alcohol consumption, n (%) No | 73 Participants |
| Alcohol consumption, n (%) Yes | 75 Participants |
| Comorbid conditions of interest, n (%) Cardiac Disease | 9 Participants |
| Comorbid conditions of interest, n (%) COPD | 4 Participants |
| Comorbid conditions of interest, n (%) Diabetes | 17 Participants |
| Comorbid conditions of interest, n (%) Hypertension | 54 Participants |
| Comorbid conditions of interest, n (%) Liver Disease | 1 Participants |
| Comorbid conditions of interest, n (%) Other | 61 Participants |
| Comorbid conditions of interest, n (%) Renal Failure | 2 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants |
| Race/Ethnicity, Customized Black or African | 11 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 120 Participants |
| Region of Enrollment Canada | 49 participants |
| Region of Enrollment United States | 103 participants |
| Sex: Female, Male Female | 148 Participants |
| Sex: Female, Male Male | 0 Participants |
| Smoker, n (%) Current | 10 Participants |
| Smoker, n (%) Never | 98 Participants |
| Smoker, n (%) Past | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 151 |
| other Total, other adverse events | 27 / 151 |
| serious Total, serious adverse events | 4 / 151 |
Outcome results
Primary
Proportion of Lymph Nodes Identified by IC2000/SPY-PHI Compared to the Proportion of Lymph Nodes Identified by Tc99m/Gamma Probe
Time frame: From Technetium-99 (Tc-99m) injection to the completion of surgery
Population: PP and mITT populations
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| IC2000/SPY-PHI | Proportion of Lymph Nodes Identified by IC2000/SPY-PHI Compared to the Proportion of Lymph Nodes Identified by Tc99m/Gamma Probe | Proportion of histology confirmed lymph nodes identified using IC2000 and SPY | 360 Lymph Nodes |
| IC2000/SPY-PHI | Proportion of Lymph Nodes Identified by IC2000/SPY-PHI Compared to the Proportion of Lymph Nodes Identified by Tc99m/Gamma Probe | Proportion of histology confirmed lymph nodes identified using Tc-99m/Gamma Probe | 266 Lymph Nodes |
Comparison: Hypothesis:~H0: QT ≤ QC - 0.05 H1: QT \> QC - 0.05p-value: <0.0001Regression, Logistic
Secondary
Proportion of Lymph Nodes Identified by IC2000/SPY-PHI by Following a Fluorescent Lymphatic Vessel, and the Proportion of Identified Lymph Nodes With no Lymphatic Vessels Visible by IC2000/SPY-PHI
Time frame: From Technetium-99 (Tc-99m) injection to the completion of surgery
Population: Total number of histology confirmed clinical lymph nodes (specimens) identified and excised by IC2000 and SPY.~\*The PP and mITT populations were identical
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| IC2000/SPY-PHI | Proportion of Lymph Nodes Identified by IC2000/SPY-PHI by Following a Fluorescent Lymphatic Vessel, and the Proportion of Identified Lymph Nodes With no Lymphatic Vessels Visible by IC2000/SPY-PHI | Proportion of Lymph Nodes Identified by IC2000 and SPY in-vivo With Lymphatic Vessel Mapping | 357 Lymph Nodes |
| IC2000/SPY-PHI | Proportion of Lymph Nodes Identified by IC2000/SPY-PHI by Following a Fluorescent Lymphatic Vessel, and the Proportion of Identified Lymph Nodes With no Lymphatic Vessels Visible by IC2000/SPY-PHI | Proportion of Lymph Nodes Identified by IC2000 and SPY in-vivo Without Lymphatic Vessel Mapping | 3 Lymph Nodes |
Secondary
Proportion of Subjects With at Least One Lymph Node Identified by IC2000/SPY-PHI, and the Proportion of Subjects With at Least One Lymph Node Identified by Tc99m/Gamma Probe
Time frame: From Technetium-99 (Tc-99m) injection to the completion of surgery
Population: PP and mITT population~\*The PP and mITT populations were identical
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IC2000/SPY-PHI | Proportion of Subjects With at Least One Lymph Node Identified by IC2000/SPY-PHI, and the Proportion of Subjects With at Least One Lymph Node Identified by Tc99m/Gamma Probe | Proportion of Subjects with At Least One Lymph Node Identified by IC2000 and SPY in-vivo | 145 Participants |
| IC2000/SPY-PHI | Proportion of Subjects With at Least One Lymph Node Identified by IC2000/SPY-PHI, and the Proportion of Subjects With at Least One Lymph Node Identified by Tc99m/Gamma Probe | Proportion of Subjects with At Least One Lymph Node Identified by Tc-99m/Gamma Probe | 145 Participants |
Secondary
To Assess the Safety of Intradermal Injection of IC2000
Number of subjects with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: From Technetium-99 (Tc-99m) injection to the completion of surgery
Population: Safety cohort (N=151)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IC2000/SPY-PHI | To Assess the Safety of Intradermal Injection of IC2000 | 3 Participants |