Cervical Cancer, Endometrial Cancer, Uterine Cancer
Conditions
Keywords
Lymph node mapping, Endometrial cancer, Uterine cancer, Cervical cancer
Brief summary
This is a randomized, prospective, open label, multicenter study to assess the safety and utility of PINPOINT® Near Infrared Fluorescence Imaging (PINPOINT) in identification of lymph nodes (LN) in patients with uterine and cervical malignancies who are undergoing LN mapping.
Interventions
DEVICEPINPOINT
PINPOINT® Near Infrared Fluorescence Imaging to identify lymph nodes
Sponsors
Novadaq Technologies ULC, now a part of Stryker
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Subjects with FIGO Clinical Stage I endometrial cancer undergoing minimally invasive hysterectomy with lymph node mapping. * Subjects with FIGO Clinical Stage IA cervical cancer ≤ 2 cm in size undergoing minimally invasive hysterectomy, trachelectomy, or conization with lymph node mapping. Subjects with clinical Stage IA1 cervical cancer without lympho vascular space involvement (LVSI) and negative margins on cone biopsy are not to be included. * Subjects with negative nodal status (N0) * Subjects with negative metastatic involvement (M0).
Exclusion criteria
* Have had prior dissection and/or radiation in pelvis. * Advanced cervical or endometrial cancer, T3/T4 lesions * Diagnosis of cervical cancer with a tumor size greater than 2 cm. * Locally advanced or inflammatory cervical or uterine cancer * Metastatic cervical or uterine cancer. * Known allergy or history of adverse reaction to ICG, iodine or iodine dyes. * Known allergy or history of adverse reaction to Blue dye (Isosulfan blue) or triphenylmethane. * Hepatic dysfunction defined as MELD Score \> 12. * Renal dysfunction defined as serum creatinine ≥ 2.0 mg/dl. * Subjects who have participated in another investigational study within 30 days prior to surgery. * Pregnant or lactating subjects. * Subjects who, in the Investigator's opinion, have any medical condition that makes the subject a poor candidate for the investigational procedure, or interferes with the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness of PINPOINT and IC2000 in the Identification of Lymph Nodes Defined as the Proportion of Confirmed Lymph Nodes Identified | Day 0 | To assess the effectiveness of intraoperative PINPOINT Near Infrared Fluorescence Imaging in the identification of lymph nodes in subjects with uterine and cervical malignancies who are undergoing lymph node mapping. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness of PINPOINT and Blue Dye in the Identification of at Least One Lymph Node Defined as the Number of Subjects in Which at Least One Confirmed Lymph Node Was Identified With Either PINPOINT or Blue Dye | Day 0 | To evaluate the effectiveness of PINPOINT and Blue dye in the identification of at least one lymph node (confirmed to be lymphoid tissue) per subject. |
| Effectiveness of PINPOINT and Blue Dye in the Identification of Bilateral Lymph Nodes Defined as the Number of Subjects in Which Lymph Nodes Were Identified Bilaterally With Either PINPOINT or Blue Dye. | Day 0 | To evaluate the effectiveness of PINPOINT and Blue dye in the identification of bilateral lymph nodes (confirmed to be lymphoid tissue). |
| Identification of Lymph Nodes Following Lymphatic Channels Defined as the Number of Subjects in Which Confirmed Lymph Nodes Were Identified by Following a Lymphatic Channel With Either PINPOINT or Blue Dye. | Day 0 | To determine the proportion of lymph nodes identified from following lymphatic channels |
| Safety of Interstitial Injection of ICG Defined as the Number of Adverse Effects Related to ICG | Day 0 to Day 30 | To assess the safety of interstitial injection of ICG for intraoperative lymphatic mapping, as measured by number of subjects experiencing adverse effects related to the study treatment. |
| Anatomic Distribution of Lymph Nodes | Day 0 | To determine the anatomic distribution of lymph nodes |
Countries
Canada, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Blue - PINPOINT The cervix will be injected 4 times with a 1ml solution of 1% Isosulfan blue followed by injection 4 times of 1 ml of 1.25 mg/ml solution of ICG. LN mapping with Blue dye will be performed until the investigator identifies all blue nodes or determines that blue nodes cannot be identified. Once complete, the Investigator will begin mapping with PINPOINT until all 'ICG' nodes are identified or the investigator determines that 'ICG' nodes cannot be identified. Once mapping with both Blue dye and PINPOINT have been completed and documented, LNs identified with Blue dye or PINPOINT will be excised.
PINPOINT: PINPOINT® Near Infrared Fluorescence Imaging to identify lymph nodes | 87 |
| PINPOINT - Blue The cervix will be injected 4 times with 1 ml of a 1.25 mg/ml solution of ICG followed by injection 4 times of a 1 ml solution of 1% Isosulfan blue. LN mapping with PINPOINT will be performed until the investigator identifies all 'ICG' nodes or determines that 'ICG' nodes cannot be identified. Once complete, the Investigator will begin mapping with Blue dye until all 'blue' nodes are identified or the investigator determines that 'blue' nodes cannot be identified. Once mapping with both Blue dye and PINPOINT have been completed and documented, LNs identified with Blue dye or PINPOINT will be excised.
PINPOINT: PINPOINT® Near Infrared Fluorescence Imaging to identify lymph nodes | 89 |
| Total | 176 |
Baseline characteristics
| Characteristic | PINPOINT - Blue | Total | Blue - PINPOINT |
|---|---|---|---|
| Age, Customized 30-39 | 4 Participants | 7 Participants | 3 Participants |
| Age, Customized 40-49 | 4 Participants | 10 Participants | 6 Participants |
| Age, Customized 50-59 | 26 Participants | 46 Participants | 20 Participants |
| Age, Customized 60-69 | 41 Participants | 74 Participants | 33 Participants |
| Age, Customized 70-79 | 12 Participants | 32 Participants | 20 Participants |
| Age, Customized >80 | 2 Participants | 7 Participants | 5 Participants |
| Alcohol Consumption No | 58 Participants | 111 Participants | 53 Participants |
| Alcohol Consumption Yes | 31 Participants | 65 Participants | 34 Participants |
| ASA Classification I - A normal healthy patient | 11 Participants | 21 Participants | 10 Participants |
| ASA Classification II - A patient with mild systemic disease | 39 Participants | 77 Participants | 38 Participants |
| ASA Classification III - A patient with severe systemic disease | 32 Participants | 66 Participants | 34 Participants |
| ASA Classification Unknown ASA Classification | 7 Participants | 12 Participants | 5 Participants |
| Cervical Cancer Histology Adenocarcinoma | 1 Participants | 4 Participants | 3 Participants |
| Cervical Cancer Histology Squamous Cell Carcinoma | 3 Participants | 3 Participants | 0 Participants |
| Endometrial Cancer Histology Adenocarcinoma | 75 Participants | 146 Participants | 71 Participants |
| Endometrial Cancer Histology Carcinosarcoma | 2 Participants | 3 Participants | 1 Participants |
| Endometrial Cancer Histology Clear Cell Carcinoma | 0 Participants | 4 Participants | 4 Participants |
| Endometrial Cancer Histology Other | 2 Participants | 3 Participants | 1 Participants |
| Endometrial Cancer Histology Serous Carcinoma | 6 Participants | 13 Participants | 7 Participants |
| Preoperative Diagnosis Stage 1A Cervical Cancer | 2 Participants | 5 Participants | 3 Participants |
| Preoperative Diagnosis Stage 1 Cervical Cancer | 2 Participants | 4 Participants | 2 Participants |
| Preoperative Diagnosis Stage 1 Endometrial Cancer | 85 Participants | 169 Participants | 84 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 73 Participants | 139 Participants | 66 Participants |
| Sex/Gender, Customized Female | 89 Participants | 176 Participants | 87 Participants |
| Smoking Status Current | 5 Participants | 7 Participants | 2 Participants |
| Smoking Status Never | 65 Participants | 131 Participants | 66 Participants |
| Smoking Status Past | 19 Participants | 38 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 89 |
| other Total, other adverse events | 13 / 87 | 10 / 89 |
| serious Total, serious adverse events | 4 / 87 | 1 / 89 |
Outcome results
Primary
Effectiveness of PINPOINT and IC2000 in the Identification of Lymph Nodes Defined as the Proportion of Confirmed Lymph Nodes Identified
To assess the effectiveness of intraoperative PINPOINT Near Infrared Fluorescence Imaging in the identification of lymph nodes in subjects with uterine and cervical malignancies who are undergoing lymph node mapping.
Time frame: Day 0
Population: All analyses were completed using the number of lymph nodes identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PINPOINT - Blue | Effectiveness of PINPOINT and IC2000 in the Identification of Lymph Nodes Defined as the Proportion of Confirmed Lymph Nodes Identified | 232 Confirmed Lymph Nodes |
| Blue - PINPOINT | Effectiveness of PINPOINT and IC2000 in the Identification of Lymph Nodes Defined as the Proportion of Confirmed Lymph Nodes Identified | 239 Confirmed Lymph Nodes |
Secondary
Anatomic Distribution of Lymph Nodes
To determine the anatomic distribution of lymph nodes
Time frame: Day 0
Population: 180 subjects were randomized. 4 subjects were found to be ineligible after randomization (subjects did not receive study treatment). Of the 176 subjects randomized who completed the study, 13 had significant protocol deviations. Thus, 163 subjects are included in the analysis population (81 subjects in the B-P arm and 82 subjects in the P-B arm).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Left obturator/internal iliac | 28 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Right external iliac | 52 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Left common iliac | 11 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Right common iliac | 17 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Left external iliac | 69 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Para-aortic node below IMA | 4 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Right obturator/internal iliac | 39 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Other | 10 confirmed lymph nodes |
| PINPOINT - Blue | Anatomic Distribution of Lymph Nodes | Presacral | 2 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Other | 7 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Presacral | 5 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Left obturator/internal iliac | 36 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Left external iliac | 67 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Left common iliac | 6 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Right obturator/internal iliac | 45 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Right external iliac | 50 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Right common iliac | 18 confirmed lymph nodes |
| Blue - PINPOINT | Anatomic Distribution of Lymph Nodes | Para-aortic node below IMA | 5 confirmed lymph nodes |
Secondary
Effectiveness of PINPOINT and Blue Dye in the Identification of at Least One Lymph Node Defined as the Number of Subjects in Which at Least One Confirmed Lymph Node Was Identified With Either PINPOINT or Blue Dye
To evaluate the effectiveness of PINPOINT and Blue dye in the identification of at least one lymph node (confirmed to be lymphoid tissue) per subject.
Time frame: Day 0
Population: 180 subjects were randomized. 4 subjects were found to be ineligible after randomization (subjects did not receive study treatment). Of the 176 subjects randomized who completed the study, 13 had significant protocol deviations. Thus, 163 subjects are included in the analysis population (81 subjects in the B-P arm and 82 subjects in the P-B arm).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PINPOINT - Blue | Effectiveness of PINPOINT and Blue Dye in the Identification of at Least One Lymph Node Defined as the Number of Subjects in Which at Least One Confirmed Lymph Node Was Identified With Either PINPOINT or Blue Dye | Isosulfan Blue | 64 Number of Subjects |
| PINPOINT - Blue | Effectiveness of PINPOINT and Blue Dye in the Identification of at Least One Lymph Node Defined as the Number of Subjects in Which at Least One Confirmed Lymph Node Was Identified With Either PINPOINT or Blue Dye | IC2000 and PINPOINT | 80 Number of Subjects |
| Blue - PINPOINT | Effectiveness of PINPOINT and Blue Dye in the Identification of at Least One Lymph Node Defined as the Number of Subjects in Which at Least One Confirmed Lymph Node Was Identified With Either PINPOINT or Blue Dye | Isosulfan Blue | 60 Number of Subjects |
| Blue - PINPOINT | Effectiveness of PINPOINT and Blue Dye in the Identification of at Least One Lymph Node Defined as the Number of Subjects in Which at Least One Confirmed Lymph Node Was Identified With Either PINPOINT or Blue Dye | IC2000 and PINPOINT | 79 Number of Subjects |
Secondary
Effectiveness of PINPOINT and Blue Dye in the Identification of Bilateral Lymph Nodes Defined as the Number of Subjects in Which Lymph Nodes Were Identified Bilaterally With Either PINPOINT or Blue Dye.
To evaluate the effectiveness of PINPOINT and Blue dye in the identification of bilateral lymph nodes (confirmed to be lymphoid tissue).
Time frame: Day 0
Population: 180 subjects were randomized. 4 subjects were found to be ineligible after randomization (subjects did not receive study treatment). Of the 176 subjects randomized who completed the study, 13 had significant protocol deviations. Thus, 163 subjects are included in the analysis population (81 subjects in the B-P arm and 82 subjects in the P-B arm).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PINPOINT - Blue | Effectiveness of PINPOINT and Blue Dye in the Identification of Bilateral Lymph Nodes Defined as the Number of Subjects in Which Lymph Nodes Were Identified Bilaterally With Either PINPOINT or Blue Dye. | IC2000 and PINPOINT | 64 Number of Subjects |
| PINPOINT - Blue | Effectiveness of PINPOINT and Blue Dye in the Identification of Bilateral Lymph Nodes Defined as the Number of Subjects in Which Lymph Nodes Were Identified Bilaterally With Either PINPOINT or Blue Dye. | Isosulfan Blue | 24 Number of Subjects |
| Blue - PINPOINT | Effectiveness of PINPOINT and Blue Dye in the Identification of Bilateral Lymph Nodes Defined as the Number of Subjects in Which Lymph Nodes Were Identified Bilaterally With Either PINPOINT or Blue Dye. | IC2000 and PINPOINT | 60 Number of Subjects |
| Blue - PINPOINT | Effectiveness of PINPOINT and Blue Dye in the Identification of Bilateral Lymph Nodes Defined as the Number of Subjects in Which Lymph Nodes Were Identified Bilaterally With Either PINPOINT or Blue Dye. | Isosulfan Blue | 25 Number of Subjects |
Secondary
Identification of Lymph Nodes Following Lymphatic Channels Defined as the Number of Subjects in Which Confirmed Lymph Nodes Were Identified by Following a Lymphatic Channel With Either PINPOINT or Blue Dye.
To determine the proportion of lymph nodes identified from following lymphatic channels
Time frame: Day 0
Population: 180 subjects were randomized. 4 subjects were found to be ineligible after randomization (subjects did not receive study treatment). Of the 176 subjects randomized who completed the study, 13 had significant protocol deviations. Thus, 163 subjects are included in the analysis population (81 subjects in the B-P arm and 82 subjects in the P-B arm).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PINPOINT - Blue | Identification of Lymph Nodes Following Lymphatic Channels Defined as the Number of Subjects in Which Confirmed Lymph Nodes Were Identified by Following a Lymphatic Channel With Either PINPOINT or Blue Dye. | IC2000 and PINPOINT | 6 Number of Subjects |
| PINPOINT - Blue | Identification of Lymph Nodes Following Lymphatic Channels Defined as the Number of Subjects in Which Confirmed Lymph Nodes Were Identified by Following a Lymphatic Channel With Either PINPOINT or Blue Dye. | Isosulfan Blue | 8 Number of Subjects |
| Blue - PINPOINT | Identification of Lymph Nodes Following Lymphatic Channels Defined as the Number of Subjects in Which Confirmed Lymph Nodes Were Identified by Following a Lymphatic Channel With Either PINPOINT or Blue Dye. | IC2000 and PINPOINT | 3 Number of Subjects |
| Blue - PINPOINT | Identification of Lymph Nodes Following Lymphatic Channels Defined as the Number of Subjects in Which Confirmed Lymph Nodes Were Identified by Following a Lymphatic Channel With Either PINPOINT or Blue Dye. | Isosulfan Blue | 6 Number of Subjects |
Secondary
Safety of Interstitial Injection of ICG Defined as the Number of Adverse Effects Related to ICG
To assess the safety of interstitial injection of ICG for intraoperative lymphatic mapping, as measured by number of subjects experiencing adverse effects related to the study treatment.
Time frame: Day 0 to Day 30
Population: 180 subjects were randomized. 4 subjects were found to be ineligible after randomization (subjects did not receive study treatment). Of the 176 subjects randomized who completed the study, 13 had significant protocol deviations. Thus, 163 subjects are included in the analysis population (81 subjects in the B-P arm and 82 subjects in the P-B arm).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PINPOINT - Blue | Safety of Interstitial Injection of ICG Defined as the Number of Adverse Effects Related to ICG | 0 Number of subjects |
| Blue - PINPOINT | Safety of Interstitial Injection of ICG Defined as the Number of Adverse Effects Related to ICG | 0 Number of subjects |