Ovarian Cancer
Conditions
Brief summary
This is a phase 3, randomized, multi-center, single dose, open label, pivotal study in patients diagnosed with, or with high clinical suspicion of, ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery.
Detailed description
The Phase 3 study is to confirm the efficacy of OTL38 in combination with fluorescent light to detect additional Folate Receptor-positive (FR+) ovarian cancer lesions not detected by palpation and visualization under normal light in patients with FR+ ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery
Interventions
DRUGOTL38
0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes
Infrared imaging used to excite OTL38 for fluorescence
PROCEDURElaparotomy
primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery
Sponsors
SynteractHCR
On Target Laboratories, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Female patients 18 years of age and older * Have a primary diagnosis, or at high clinical suspicion, of primary ovarian cancer (of epithelial type), planned for primary surgical cytoreduction, interval debulking, or have recurrent ovarian cancer surgery, and: * Who are scheduled to undergo laparotomy for the debulking surgery OR * Who are scheduled to undergo laparoscopy and pre-authorized to undergo laparotomy for the debulking surgery if cancer is detected on the laparoscopy * A negative serum pregnancy test at Screening followed by a negative urine pregnancy test on the day of surgery or day of admission for female patients of childbearing potential * Female patients of childbearing potential or less than 2 years postmenopausal agree to use an acceptable form of contraception from the time of signing informed consent until 30 days after study completion * Ability to understand the requirements of the study, provide written informed consent for participation in the study and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments
Exclusion criteria
* Previous exposure to OTL38 * Known FR-negative ovarian cancer * Planned surgical debulking via laparoscopy or robotic surgery, with no intent of laparotomy. * Patients with known ovarian cancer miliary disease determined preoperatively to be inoperable. * Any medical condition that, in the opinion of the investigators, could potentially jeopardize the safety of the patient * History of anaphylactic reactions * History of allergy to any of the components of OTL38, including folic acid * Pregnancy or positive pregnancy test * Clinically significant abnormalities on electrocardiogram (ECG) * Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * Impaired renal function defined as eGFR\< 50 mL/min/1.73m2 * Impaired liver function defined as values \> 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin. * Known Stage IV ovarian cancer with brain metastases * Received an investigational agent in another clinical trial within 30 days prior to surgery * Known sensitivity to fluorescent light
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Patient Level | 30 days | Percentage of patients with at least one evaluable FR+ ovarian cancer lesion confirmed by central pathology (Standard of truth) that was detected using the combination of OTL38 and fluorescent light but not under normal light or palpation (Full Analysis Set) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient False Positive Rate | 30 days | False Positive Rate at the patient level (FPRp) will be a major secondary efficacy endpoint and is defined as the percentage of women who underwent both normal light and fluorescent light (Intent-to-Image Set) |
Countries
Netherlands, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental: OTL38 Injection and Near Infrared Imaging Patient injected with OTL38 and undergoes near infrared imaging.
Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes
Other Names:
OTL38 for Injection Device: near infrared camera imaging system Infrared imaging used to excite OTL38 for fluorescence
Other Names:
Near IR imaging Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery | 134 |
| Sham Comparator: OTL38 Injection and No Fluorescent Imaging Patient injected with OTL38, but does not undergo fluorescent imaging.
Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes
Other Names:
OTL38 for Injection
Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery | 6 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Majority of which were disease too extensive and camera not used | 3 | 0 |
Baseline characteristics
| Characteristic | Sham Comparator: OTL38 Injection and No Fluorescent Imaging | Total | Experimental: OTL38 Injection and Near Infrared Imaging |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 21.77 | 60.8 years STANDARD_DEVIATION 11.39 | 60.4 years STANDARD_DEVIATION 10.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 17 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 120 Participants | 116 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 5 Participants | 119 Participants | 114 Participants |
| Sex: Female, Male Female | 6 Participants | 140 Participants | 134 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 150 |
| other Total, other adverse events | 34 / 150 |
| serious Total, serious adverse events | 22 / 150 |
Outcome results
Primary
Efficacy Patient Level
Percentage of patients with at least one evaluable FR+ ovarian cancer lesion confirmed by central pathology (Standard of truth) that was detected using the combination of OTL38 and fluorescent light but not under normal light or palpation (Full Analysis Set)
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set | Efficacy Patient Level | 26.9 percentage of participants |
Secondary
Patient False Positive Rate
False Positive Rate at the patient level (FPRp) will be a major secondary efficacy endpoint and is defined as the percentage of women who underwent both normal light and fluorescent light (Intent-to-Image Set)
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set | Patient False Positive Rate | 20.2 percentage of participants |