Breast Cancer, Colorectal Cancer, Head and Neck Squamous Cell Carcinoma, Non-small Cell Lung Cancer, Ovarian Cancer, Prostate Cancer, Urothelial Carcinoma
Conditions
Brief summary
This study is to evaluate diagnostic performance, safety and timing of post-dose imaging of ONM-100, an intraoperative fluorescence imaging agent for the detection of cancer in patients with solid tumors undergoing routine surgery.
Interventions
DRUGONM-100
A polymer micelle covalently conjugated to indocyanine green.
Sponsors
OncoNano Medicine, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy-confirmed diagnosis of primary or recurrent respective tumor type and scheduled to undergo surgical resection * Part 1: Biopsy-confirmed diagnosis of head and neck squamous cell carcinoma (HNSCC) or breast cancer * Part 2: Biopsy-confirmed diagnosis of HNSCC, breast cancer, colorectal cancer, prostate cancer, ovarian cancer, urothelial carcinoma and non-small cell lung cancer. * Part 3: Stage 2 to 4 HNSCC Including T0 or Tx unknown Primary cancers
Exclusion criteria
* Histologically diagnosed by an excisional biopsy procedure * Tumors at sites of which the surgeon would assess that in vivo intraoperative imaging would not be feasible * Life expectancy \<12 weeks * Hepatic impairment (Child-Pugh score \>5) or significant liver disease including active hepatitis or cirrhosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)] | 1 day | Part 1: Evaluate the dose(s) at which ONM-100 fluorescence imaging is feasible at 3±2 hours post dose. Part 2: Verify the safety and diagnostic performance of ONM-100 compared to standard pathology at the dose(s) and imaging schedule(s) post dose selected from Part 1 for the detection of primary tumors and the metastatic lymph nodes in a variety of solid cancers (which could have included HNSCC, breast cancer, colorectal cancer, urothelial cancer, prostate cancer, ovarian cancer, and/or non-small cell lung carcinoma \[NSCLC\]). Part 3: Assess the safety and efficacy (sensitivity and positive predictive value \[PPV\] of ONM-100 for intraoperative imaging during HNSCC surgery. |
| Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28 | 28 days | Evaluate safety at the dose(s) used to assess imaging feasibility and select the dose(s) and imaging schedule(s) post dose that are safe and provide optimal imaging of solid tumors and metastatic lymph nodes; the dose and time post dose chosen for the detection of primary tumors and metastatic lymph nodes could be the same or different. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Pharmacokinetic Parameters: AUC | 6 days | Evaluate the Area under the time-concentration curve \[AUC\] of ONM-100 at 1 mg/kg, 2 mg/kg, and 3 mg/kg doses. |
| Evaluate Pharmacokinetic Parameters: CL | 6 days | Evaluate Total body clearance \[CL\] of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2. |
| Evaluate Pharmacokinetic Parameters: Cmax | 6 days | Evaluate the maximum plasma concentration (Cmax) of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging at doses of 1 mg/kg, 2 mg/kg and 3 mg/kg. |
| Evaluate Pharmacokinetic Parameters: t1/2 | 6 days | Evaluate the Terminal elimination half-life \[t1/2\] of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2. |
| Evaluate Pharmacokinetic Parameters: Vz | 6 days | Evaluate the Volume of distribution \[Vz\] of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2. |
| Evaluate Pharmacokinetic Parameters: Tmax | 6 days | Evaluate the time to Cmax (Tmax) of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Cohort A Patients were administered a single dose of pegsitacianine (ONM-100) at 1.0 mg/kg and underwent surgery and fluorescence imaging at 3 ±2 hours post dose. | 3 |
| Part 1, Cohort B Patients were administered a single dose of pegsitacianine (ONM-100) at 3.0 mg/kg and underwent surgery and fluorescence imaging at 3 ±2 hours post dose. | 3 |
| Part 1, Cohort E Patients were administered a single dose of pegsitacianine (ONM-100) at 2 mg/kg and underwent surgery and fluorescence imaging at 6 ±3 hours post dose. | 3 |
| Part 2, Group 2 Patients were administered a single dose of pegsitacianine (ONM-100) at 3 mg/kg and underwent surgery and fluorescence imaging at a time to be determined post dose. | 4 |
| Part 2, Group 3 Patients were administered a single dose of pegsitacianine (ONM-100) at 1 mg/kg and underwent surgery and fluorescence imaging at 16-80 hours post dose. | 6 |
| Part 3 Patients were administered a single dose of pegsitacianine (ONM-100) at 1 mg/kg and underwent surgery and fluorescence imaging at 24 ±8 hours post dose. | 11 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Patient unable or unwilling to continue | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1, Cohort A | Part 1, Cohort B | Part 1, Cohort E | Part 2, Group 2 | Part 2, Group 3 | Part 3 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.0 years STANDARD_DEVIATION 8.19 | 63.7 years STANDARD_DEVIATION 3.79 | 59.3 years STANDARD_DEVIATION 15.31 | 65.5 years STANDARD_DEVIATION 5.07 | 59.8 years STANDARD_DEVIATION 4.71 | 59.8 years STANDARD_DEVIATION 10.26 | 60.5 years STANDARD_DEVIATION 8.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 10 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Patients receiving pegsitacianine (ONM-100) | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 6 Participants | 11 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 5 Participants | 7 Participants | 22 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 3 participants | 4 participants | 6 participants | 11 participants | 30 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 6 Participants | 8 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 6 | 0 / 11 |
| other Total, other adverse events | 2 / 3 | 3 / 3 | 2 / 3 | 4 / 4 | 4 / 6 | 9 / 11 |
| serious Total, serious adverse events | 0 / 3 | 2 / 3 | 0 / 3 | 1 / 4 | 0 / 6 | 3 / 11 |
Outcome results
Primary
Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28
Evaluate safety at the dose(s) used to assess imaging feasibility and select the dose(s) and imaging schedule(s) post dose that are safe and provide optimal imaging of solid tumors and metastatic lymph nodes; the dose and time post dose chosen for the detection of primary tumors and metastatic lymph nodes could be the same or different.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohort A | Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28 | 2 Participants |
| Part 1, Cohort B | Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28 | 3 Participants |
| Part 1, Cohort E | Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28 | 2 Participants |
| Part 2, Group 2 | Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28 | 4 Participants |
| Part 2, Group 3 | Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28 | 6 Participants |
| Part 3 | Incidence Rate of All Treatment-emergent Adverse Events (TEAEs) From Time of ONM-100 Administration Through Day 28 | 9 Participants |
Primary
Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)]
Part 1: Evaluate the dose(s) at which ONM-100 fluorescence imaging is feasible at 3±2 hours post dose. Part 2: Verify the safety and diagnostic performance of ONM-100 compared to standard pathology at the dose(s) and imaging schedule(s) post dose selected from Part 1 for the detection of primary tumors and the metastatic lymph nodes in a variety of solid cancers (which could have included HNSCC, breast cancer, colorectal cancer, urothelial cancer, prostate cancer, ovarian cancer, and/or non-small cell lung carcinoma \[NSCLC\]). Part 3: Assess the safety and efficacy (sensitivity and positive predictive value \[PPV\] of ONM-100 for intraoperative imaging during HNSCC surgery.
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Cohort A | Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)] | 1.098 ratio | Standard Deviation 0 |
| Part 1, Cohort B | Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)] | 4.022 ratio | Standard Deviation 2.8139 |
| Part 1, Cohort E | Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)] | 2.280 ratio | Standard Deviation 1.6393 |
| Part 2, Group 2 | Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)] | 4.110 ratio | Standard Deviation 1.2527 |
| Part 2, Group 3 | Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)] | 3.007 ratio | Standard Deviation 1.3822 |
| Part 3 | Measure Mean Fluorescence Intensity of Histologically Confirmed Tumor vs Normal Tissue in Patients Undergoing Routine Surgery [Tumor to Background Ratio (TBR)] | 2.608 ratio | Standard Deviation 2.5936 |
Secondary
Evaluate Pharmacokinetic Parameters: AUC
Evaluate the Area under the time-concentration curve \[AUC\] of ONM-100 at 1 mg/kg, 2 mg/kg, and 3 mg/kg doses.
Time frame: 6 days
Population: The PK analysis population comprised 19 patients for whom concentration data were available. Due to sparse plasma concentrations for the majority of patients, with the exception of Cmax and Tmax, it was not possible to estimate all parameters for all patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Cohort A | Evaluate Pharmacokinetic Parameters: AUC | 433 hr x μg/mL | Geometric Coefficient of Variation 127 |
| Part 1, Cohort B | Evaluate Pharmacokinetic Parameters: AUC | 1509 hr x μg/mL | Geometric Coefficient of Variation 80.1 |
| Part 1, Cohort E | Evaluate Pharmacokinetic Parameters: AUC | 2067 hr x μg/mL | Geometric Coefficient of Variation 38.4 |
Secondary
Evaluate Pharmacokinetic Parameters: CL
Evaluate Total body clearance \[CL\] of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2.
Time frame: 6 days
Population: The PK analysis population comprised 19 patients for whom concentration data were available. Due to the sparse plasma concentrations for the majority of patients, with the exception of Cmax and Tmax, it was not possible to estimate all parameters for all patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Cohort A | Evaluate Pharmacokinetic Parameters: CL | 0.053 L/hr | Geometric Coefficient of Variation 2.57 |
| Part 1, Cohort E | Evaluate Pharmacokinetic Parameters: CL | 0.053 L/hr | Geometric Coefficient of Variation 70.5 |
Secondary
Evaluate Pharmacokinetic Parameters: Cmax
Evaluate the maximum plasma concentration (Cmax) of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging at doses of 1 mg/kg, 2 mg/kg and 3 mg/kg.
Time frame: 6 days
Population: The PK analysis population is comprised 19 patients for whom concentration data were available. Due to sparse plasma concentrations for the majority of patients, with the exception of Cmax and Tmax, it was not possible to estimate all parameters for all patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Cohort A | Evaluate Pharmacokinetic Parameters: Cmax | 26.5 μg/mL | Geometric Coefficient of Variation 16 |
| Part 1, Cohort B | Evaluate Pharmacokinetic Parameters: Cmax | 52.2 μg/mL | Geometric Coefficient of Variation 13 |
| Part 1, Cohort E | Evaluate Pharmacokinetic Parameters: Cmax | 79.5 μg/mL | Geometric Coefficient of Variation 30 |
Secondary
Evaluate Pharmacokinetic Parameters: t1/2
Evaluate the Terminal elimination half-life \[t1/2\] of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2.
Time frame: 6 days
Population: The PK analysis population comprised 19 patients for whom concentration data were available. Due to the sparse plasma concentrations for the majority of patients, with the exception of Cmax and Tmax, it was not possible to estimate all parameters for all patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Cohort A | Evaluate Pharmacokinetic Parameters: t1/2 | 49.0 hr | Geometric Coefficient of Variation 36.7 |
| Part 1, Cohort E | Evaluate Pharmacokinetic Parameters: t1/2 | 69.4 hr | Geometric Coefficient of Variation 8.8 |
Secondary
Evaluate Pharmacokinetic Parameters: Tmax
Evaluate the time to Cmax (Tmax) of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2.
Time frame: 6 days
Population: The PK analysis population comprised 19 patients for whom concentration data were available. Due to sparse plasma concentrations for the majority of patients, with the exception of Cmax and Tmax, it was not possible to estimate all parameters for all patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Cohort A | Evaluate Pharmacokinetic Parameters: Tmax | 0.25 hr |
| Part 1, Cohort B | Evaluate Pharmacokinetic Parameters: Tmax | 0.31 hr |
| Part 1, Cohort E | Evaluate Pharmacokinetic Parameters: Tmax | 0.31 hr |
Secondary
Evaluate Pharmacokinetic Parameters: Vz
Evaluate the Volume of distribution \[Vz\] of ONM-100 at the dose(s) and imaging schedule(s) post dose used to assess optimal imaging in Part 1 and Part 2.
Time frame: 6 days
Population: The PK analysis population comprised 19 patients for whom concentration data were available. Due to sparse plasma concentrations for the majority of patients, with the exception of Cmax and Tmax, it was not possible to estimate all parameters for all patients.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Cohort A | Evaluate Pharmacokinetic Parameters: Vz | 3.78 L | Geometric Coefficient of Variation 33.9 |
| Part 1, Cohort E | Evaluate Pharmacokinetic Parameters: Vz | 5.32 L | Geometric Coefficient of Variation 82.9 |