Primary* 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…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
- Obstetric and gynaecological therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy:
* Proportion 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. All evaluable FR+ ovarian cancer lesions that were identified prior
to or after surgery, that were detected using the combination of OTL38 and
fluorescent light but not under normal light or palpation, and were removed
based on the evaluation under fluorescent light, will be included in the
calculation of the proportion of patients with at least one FR+ ovarian cancer
lesion confirmed by central pathology. The primary endpoint will be determined
based on evaluable lesions as described below.
* Evaluable lesions are defined as follows: lesions that do not appear on an
organ or tissue that was intended for removal based on the Pre-Fluorescence
Surgical Plan, regardless of the absence or presence of tumor.
Secondary outcome
Secondary Efficacy:
* False Positive Rate at the patient level (FPRp) will be a major secondary
efficacy endpoint and is defined as the proportion of folate positive ovarian
cancer patients in whom all lesions, without regard to evaluable lesion status,
detected by fluorescent light only, are histologically negative.
* Sensitivity or True Positive Rate (TPR) for OTL38 in combination with
fluorescent light, defined as the proportion of fluorescent light positive
lesions that are histologically confirmed to be FR+ and ovarian cancer by
central pathology relative to the total number of lesions confirmed to be FR+
and ovarian cancer by central pathology without regard to evaluable lesion
status. From the classification table below: TP/TP+FN
* False positive rate (FPR) for OTL38 in combination with fluorescent light,
for the purpose of this protocol, will be calculated as 1 * the Positive
Predictive Value (PPV) and is defined as the proportion of fluorescent light
positive lesions removed that are histologically confirmed to be non-cancerous,
or if cancerous, not FR+ and ovarian cancer, by central pathology relative to
the total number of lesions removed with fluorescent light imaging without
regard to evaluable lesion status.
Background summary
Ovarian cancer is the twelfth leading cause of cancer death in the United
States. Based on data from SEER 18 2006-2012, the overall five-year survival
rate is 46.2% and for distant and unstaged disease it is only 24-28% (SEER
2016; Kosary 2007). The standard management of primary ovarian cancer is
optimal cytoreductive surgery (usually defined as reduction of residual disease
to less than 1 to 2 cm) followed by chemotherapy (Al Rawahi 2013). Experts are
advocating complete cytoreductive surgery for tumor debulking as it results in
better overall survival than optimal cytoreduction (Shih 2010). Although tumor
debulking surgery is the cornerstone of current treatment in patients, the
lesions can be diffuse and numerous, of various sizes, and often not readily
visible in the surgical field, leading to varying rates of optimal
cytoreduction among surgeons (Ibeanu 2010). This is an important factor in the
poor prognosis for patients with advanced ovarian cancer. Tumor-specific
intraoperative fluorescence imaging may improve staging and debulking efforts
in cytoreductive surgery.
Study objective
Primary
* 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
Secondary
* To estimate the proportion of folate positive ovarian cancer patients in whom
all lesions detected by fluorescent light only are histologically negative, the
patient level False Positive Rate (FPRp)
* To estimate the Sensitivity and False Positive Rate for OTL38 in combination
with fluorescent light with respect to the detection of FR+ ovarian cancer
lesions confirmed by central pathology
* To assess the safety of using OTL38 and Visionsense VS3 Imaging System for
intraoperative imaging with OTL38
Exploratory
* To estimate the lesion inoperability rate for all lesions identified by
fluorescent light only.
* To describe the diagnostic characteristics of OTL38 in combination with
fluorescent light for lesions of various histological and pathological cell
types
* To assess CA-125 levels before and after surgery
* To estimate the plasma pharmacokinetics (PK) of OTL38 in patients with FR+
ovarian cancer scheduled to undergo primary surgical cytoreduction, interval
debulking, or recurrent ovarian cancer surgery
Study design
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.
All patients participating in the study are expected to receive OTL38 and
undergo normal light evaluation; however, to guard against the possible *under-
calling* of lesions during the normal light assessment, a small number of
patients will be randomized to a no fluorescent imaging group. All patients
will first undergo evaluation by normal light and all suspicious lesions
identified under normal white light will be recorded as such. Following normal
light assessment, but prior to any surgical removal of lesions or the use of
fluorescent light imaging, patients will be randomized to either undergo
fluorescent imaging or not. Patients randomized to the no fluorescent imaging
group receive the usual standard of care and surgery based on normal light
assessment only. Patients randomized to the fluorescent imaging group will
undergo assessment with fluorescent light imaging prior to and after surgery.
The randomized allocation ratio of normal light and fluorescent imaging
patients to normal light only patients will remain blinded to the Investigators
and their staff. Please see Section 5.7.1.2. for details regarding surgical
procedures and imaging data collection.
Prior to the surgery, the clinician will develop an initial Pre-Fluorescence
Surgical Plan for the patient based on medical history, physical examination
and laboratory evaluation, including imaging studies such as CT, PET and/or
MRI. The clinician will confirm and record this Pre-Fluorescence Surgical Plan
at the time of surgery based on their evaluation of the patient under normal
white light only, and prior to fluorescent imaging. Any changes to the
Pre-Fluorescence Surgical Plan based on fluorescent light imaging, both prior
to initiation of the surgical procedure and upon reimaging of the surgical
field after the surgical procedure immediately prior to surgical closure, will
be recorded in the case report forms.
Efficacy will be assessed for patients undergoing both normal light and
fluorescent light imaging. All patients exposed to OTL38, regardless of
randomized group assignment, will be followed for safety. The study will
consist of a screening period of up to 28 days prior to the scheduled surgery,
a diagnosis and treatment period (day of surgery; Day 1), and safety assessment
visits on Day 7 (+/-4) and Day 28 (+/-4) after surgery. The study database will
be frozen when the last patient completes the Day 28 assessment (which will be
considered the study completion date); AEs will not be monitored after the
study completion date. Long-term follow-up data on CA-125 levels will be
collected 6 months after surgery from available patients
Intervention
Administration of OTL38 and use of a fluorescent imaging system during surgery.
Study burden and risks
Risks:
Hypersensitivity reactions
Risks of taking blood samples: pain, bruising, infection
Presence of a camera system in the operating room
Burden:
Extra time investment
The risks of participation for the subjects in the trial include
hypersensitivity reactions. These risks are deemed minimal.
Nevertheless precautionary measures (supervised administration by qualified
staff and availability of medical treatment to
treat hypersensitivity reactions) are in place and these effects are generally
well manageable. The burden of the trial is
minimal, the research will for the largest part coincide with routine care and
the proposed procedures are minimally
invasive. We therefore believe this research that, could possibly provide a
useful tool to reduce positive resection margins
hence reducing rates of re-interventions increase the identification rate of
otherwise occult malignant lesions and possibly
improves patient outcome and may be used in staging procedures, is justified.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
1. Female patients 18 years of age and older
2. 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:
o Who are scheduled to undergo laparotomy for the debulking surgery OR
o Who are scheduled to undergo laparoscopy and pre-authorized to undergo laparotomy for the debulking surgery if cancer is detected on the laparoscopy
3. 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
4. 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
5. 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
Exclusion criteria
1. Previous exposure to OTL38
2. Known FR-negative ovarian cancer
3. Planned surgical debulking via laparoscopy or robotic surgery, with no intent of laparotomy.
4. Patients with known ovarian cancer miliary disease prior to surgery
5. Any medical condition that, in the opinion of the investigators, could potentially jeopardize the safety of the patient
6. History of anaphylactic reactions
7. History of allergy to any of the components of OTL38, including folic acid
8. Pregnancy or positive pregnancy test
9. Clinically significant abnormalities on electrocardiogram (ECG)
10.Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
11.Impaired renal function defined as eGFR< 50 mL/min/1.73m2
12.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.
13.Known Stage IV ovarian cancer with brain metastases
14.Received an investigational agent in another clinical trial within 30 days prior to surgery
15.Known sensitivity to fluorescent light
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-004255-20-NL |
| CCMO | NL68086.056.18 |
| OMON | NL-OMON27574 |