Primary Objectives1. To assess the safety and tolerability of ascending doses of a single IV injection of OTL-0382. To assess the efficacy of ascending doses of a single IV injection of OTL-038 in detecting ovarian, renal cell and endometrial cancer…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy endpoints
1. TBR, defined as fluorescent signal of tumor tissue compared to fluorescence
signal of tissue surrounding the tumor, at different doses;
2. Concordance between the pathology results with respect to the presence of
cancer and the imaging assessment;
3. Number and location of FR-a+, cancer+ tumor lesions or resection margins
identified under usual visual/tactile conditions, under both usual
visual/tactile conditions and fluorescent light, and under fluorescent light
only
4. Surgeons* opinion regarding utility of IV OTL-038 injection and imaging
system
Tolerability / safety endpoints
Treatment-emergent adverse events (TEAEs) using MedDRA from the time of
administration throughout the study period, and changes in serum biochemistry,
hematology, urinalysis, vital signs, ECG, injection site status, and physical
examination findings.
Pharmacokinetic endpoints
Cmax, T*, AUC, Tmax, Clearance, urinary excretion
Secondary outcome
n/a
Background summary
It is important to improve visualization of tumors and metastases, such as in
ovarian, renal cell and endometrial cancer, in real time during surgery to
enable the surgeon to excise more of the tumor, and also to facilitate proper
staging. Intra-operative identification of cancer tissue using new real-time
imaging modalities that could provide clear tumor identification and
demarcation would provide a very useful tool to reduce positive resection
margins and increase full removal of the tumor hence reducing rates of
re-interventions and therefore may reduce morbidity and improve patient
outcome. Furthermore, if otherwise invisible tumor lesions and metastasis can
be identified, tumor staging will be possibly improved which influences
treatment choices. In the last few years, a novel optical imaging platform has
emerged. The use of fluorescent probes that recognize cancer-specific antigens,
in conjunction with a clinical imaging system, are under investigation.
OTL-038, a fluorescent probe that targets FR-a, a receptor over-expressed in
most ovarian, renal cell and high risk endometrial cancers, and that emits
lights with wavelengths in the near-infrared (NIR) spectrum, along with an
imaging system, can be used to visualize folate receptor alpha (FR-a) positive
cancer in patients during surgery. This could enable the surgeon to excise more
of the tumor tissue as compared to usual visual and tactile methods.
Study objective
Primary Objectives
1. To assess the safety and tolerability of ascending doses of a single IV
injection of OTL-038
2. To assess the efficacy of ascending doses of a single IV injection of
OTL-038 in detecting ovarian, renal cell and endometrial cancer during surgery
by :
a. Tumor to background ratio (TBR)
b. Concordance between fluorescent signal and tumor status of resected tissue
c. Detection of more FR-a+, cancer+ tumor lesions and resection margins with
fluorescent light compared to usual visual/tactile conditions
3. To assess the surgeons* opinion regarding the utility of OTL-038 IV
injection and imaging system in cancer surgery
4. To assess the pharmacokinetics of ascending doses of a single IV injection
of OTL-038
Exploratory Objectives
1. To assess the efficacy of different imaging systems ex-vivo by
a. Back table TBR
Study design
Phase 2, open-label, exploratory study
Study burden and risks
Risks
Hypersensitivity reactions
Risks of taking blood sample: pain, bruising, infection
Presence of a camera 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 and increase the
identification rate of otherwise occult malignant lesions and possibly improves
patient outcome and may be used in staging procedures, is justified.
Win Hentschel Blvd 1281
West-Lafayette Indiana 47906
US
Win Hentschel Blvd 1281
West-Lafayette Indiana 47906
US
Listed location countries
Age
Inclusion criteria
Inclusion criteria ovarian cancer:
1. Known or high clinical suspicion of primary ovarian cancer planned for either primary debulking surgery or interval debulking surgery by laparotomy (18 patients)
2. Clinical suspicion of primary ovarian cancer planned for either laparoscopic staging procedure or laparoscopic procedure to determine optimal primary treatment (debulking surgery procedure vs neo-adjuvant chemotherapy) (15 patients);Inclusion criteria renal cell cancer:
1. Known or high clinical suspicion of primary renal cell carcinoma planned for either primary radical nephrectomy by laparotomy or laparoscopy (3 patients) or partial nephrectomy by laparoscopy (15 patients)
Inclusion criteria endometrial cancer:
1. Known or high clinical suspicion of primary endometrial carcinoma planned for either primary staging or debulking surgery by laparotomy or laparoscopy (15 patients)
Inclusion criteria general:
1. 18 years of age and older
2. Normal or clinically acceptable medical history, physical examination (including vital signs), and laboratory tests at screening
3. Patients are clinically fit for surgery
Exclusion criteria
1. Any condition that in the opinion of the investigators could potentially jeopardize the health status of the patient
2. History of anaphylactic reactions or severe allergies
3. History of allergy to any of the components of OTL-038, including folic acid
4. Pregnancy, or positive pregnancy test
5. Clinically significant abnormalities in ECG and/or clinical laboratory test results
6. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
7. Impaired renal function defined as eGFR<50 ml/min/1.73m2
8. Impaired liver function defined as values greater than 3x the upper limit of normal (ULN) for ALT, AST, or total bilirubin.
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-002352-12-NL |
| CCMO | NL49686.058.14 |