Part A: healthy volunteers (n=up to 15)Primary/safety objective: - To assess the safety, tolerability and pharmacokinetics of a single IV dosage of OTL78 Secondary objective: - To assess the pharmacodynamics of OTL78 by measuring the temporal…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A: healthy volunteers (n= up to 15)
Primary/safety objective:
- To assess the safety, tolerability and pharmacokinetics of a single IV
dose of OTL78
Part B/part C: patients (n=24)
Primary/safety objective:
- To assess the safety, tolerability and pharmacokinetics of a single IV dose
of OTL78
Secondary outcome
Part A: healthy volunteers (n= up to 15)
Secondary objective:
- To assess the pharmacodynamics of OTL78 by measuring the temporal
relationship of fluorescence of superficial tissues (skin/veins and mucosa).
Part B/Part C: patients (n=24)
Secondary objectives:
- To estimate the Sensitivity (or True Positive rate, TP/(TP+FN)) of OTL78 for
detection of tissues expressing PSMA or prostate cancer during near infrared
imaging (NIR)
- To estimate the Specificity (or True Negative rate, TN/(TN+FP)) of OTL78 for
detection of PSMA+ tissue and prostate cancer cells during near infrared
imaging (NIR)
- To estimate the False Positive rate (FP/(FP+TN)) of OTL78 for detection of
tissues expressing PSMA or prostate cancer during near infrared imaging (NIR)
- To estimate the False Negative rate (FN/(FN+TP)) of OTL78 for detection of
PSMA+ tissues prostate cancer cells during near infrared imaging (NIR)
- To evaluate the tumor to background ratio (TBR)
Exploratory Objective:
- To evaluate the surgeons* rating for the utility of OTL78 IV injection and
imaging system in visualizing prostate cancer and/or lymph nodes during surgery
Background summary
Surgery is the mainstay in the initial treatment of many solid tumors. Complete
resection has shown to be an important prognostic indicator for survival.
However, this can be challenging when the surgical field is observed with the
naked eye only. Therefore, agents that improve tumor identification and the
likelihood of complete resection are being developed. These agents are directed
towards tumor-specific targets and emit light at non-visible wavelengths. By
using near-infrared (NIR) camera systems, they may enable detection of
malignant tissues and distinguish them from normal tissue. OTL78 is an imaging
agent that specifically binds to the PSMA (prostate specific membrane antigen)
which is expressed on prostate cells, particularly cancer and possibly involved
lymph nodes. Intra-operative identification of cancer tissue using real-time
imaging modalities that could improve tumor identification and demarcation
would provide a very useful tool to reduce the frequency of positive resection
margins and increase complete removal of locally spread tumor and involved
lymph nodes. Complete removal of cancer and metastases may in turn reduce rates
of re- interventions and therefore morbidity to help improve patient outcomes.
As there is no clinical experience with OTL78, the study drug will first be
studied in healthy volunteers and subsequently in patients to assess the
safety, tolerability and pharmacokinetics The performance of OTL78 in
intraoperative imaging of prostate cancer will be assessed in (Part B/part C,
proof of concept).
Study objective
Part A: healthy volunteers (n=up to 15)
Primary/safety objective:
- To assess the safety, tolerability and pharmacokinetics of a single IV dosage
of OTL78
Secondary objective:
- To assess the pharmacodynamics of OTL78 by measuring the temporal
relationship of fluorescence of superficial tissues (skin/veins and mucosa).
Part B: patients (n=24)
Primary/safety objective:
- To assess the safety, tolerability and pharmacokinetics of a single IV dose
of OTL78
Secondary objectives:
- To estimate the Sensitivity (or True Positive rate, TP/(TP+FN)) of OTL78 for
detection of tissues expressing PSMA during near infrared imaging (NIR)
- To estimate the Specificity (or True Negative rate, TN/(TN+FP)) of OTL78 for
detection of prostate cancer cells during near infrared imaging (NIR)
- To estimate the False Positive rate (FP/(FP+TN)) of OTL78 for detection of
tissues expressing PSMA during near infrared imaging (NIR)
- To estimate the False Negative rate (FN/(FN+TP)) of OTL78 for detection of
prostate cancer cells during near infrared imaging (NIR)
- To evaluate the tumor to background ratio (TBR)
Exploratory Objective:
- To evaluate the surgeons* rating for the utility of OTL78 IV injection and
imaging system in visualizing prostate cancer and/or lymph nodes during surgery
Study design
Part A (healthy volunteers)
This is a single ascending dose, double-blind, randomized, placebo-controlled
design in 10 healthy volunteers. Two ascending dose levels of OTL78 (0.03mg/kg
and 0.06mg/kg) will be investigated in two consecutive cohorts. Placebo will
consist of 5% dextrose. To ensure blinding, 5% dextrose fluid bags containing
active drug or placebo will be wrapped in foil.
Part B (patients)
This is a single dose, open label, exploratory (proof of concept) study in up
to 6 patients with prostate cancer who have been scheduled to undergo a pelvic
lymph node dissection for (primairy or recurrent) prostate cancer. Each
surgical procedure will be performed with the DaVinci Xi according to standard
of care. The dose of OTL78, determined and approved as the highest tolerated
dose in Part A (0.06 mg/kg), will be administered. Surgery will take place at
least 1 hour after the end of the infusion.
If there is too much background signal in the first 3 patients, the dose is
de-escalated from 0.06 mg/kg to 0.03 mg / kg for the following 3 patients. If
the fluorescent signal is adequate, the 0.06 mg / kg dose is maintained.
If insufficient fluorescent signal is measured, part B is paused and part A is
expanded with a third dose cohort with healthy volunteers (0.12 mg / kg),
following the same approach as previous dose cohorts. If this dose is found to
be safe and has been approved by the BEBO, part B will be restarted with this
dose.
A systematic approach is also designed for use of the different near-infrared
cameraystems.
Follow-up phone call will take place +/- 2 weeks after OTL78- administration.
Part C:
This is a single dose, open label, exploratory (proof of concept) study in up
to 18 patients with prostate cancer who have been scheduled to undergo a
prostatectomy (Gleason score 7+). Each surgical procedure will be performed
with the DaVinci Xi according to standard of care. The dose of OTL78,
determined and approved as the highest tolerated dose in Part A (0.06 mg/kg),
will be administered. Surgery will take place at least 1 hour after the end of
the infusion.
if there is too much background signal in the first 3 patients, the dose is
de-escalated from 0.06 mg/kg to 0.03 mg / kg for the following patients. If the
fluorescent signal is adequate, the 0.06 mg / kg dose is maintained. If
insufficient fluorescent signal is measured, part C is paused and part A is
expanded with a third dose cohort with healthy volunteers (0.12 mg / kg),
following the same approach as previous dose cohorts. If this dose is found to
be safe and has been approved by the BEBO, part C will be restarted with this
dose.
A systematic approach is also designed for use of the different near-infrared
cameraystems.
Follow-up phone call will take place +/- 2 weeks after OTL78- administration.
Intervention
OTL78
Study burden and risks
There are no expected direct benefits to the healthy volunteers (part A) or
patients (part B/part C) who participate in the study. However, the
participants may help others prospectively by contributing to the knowledge
base for designing future studies with OTL78 in patients with prostate cancer.
The risks to participants related to OTL78 are currently unknown. Although DUPA
and the fluorescent dye OTL have clinical data with no safety signals to date,
the risk of hypersensitivity reactions for OTL78 is unknown. During the
administration of OTL0078, interruption of the infusion and/or treatment with
an anti-histamine may be required in subjects who experience symptoms
suggestive of hypersensitivity, followed by an observational period until the
symptoms resolve. Symptoms to be aware of may include but are not limited to
flushing, nausea, vomiting, abdominal pain and pruritis/urticaria. Other risks
to subjects may include injection site adverse reactions (infusion and venous
blood sampling), such as infection and hematoma. The use of a near-infrared
fluorescence camera system during surgery (part B/part C) may result in, but
not limited to, contamination of the sterile field or injury due to
disengagement of the imaging device component coming in contact with the
patient and/or surgical team.
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Age
Inclusion criteria
Healthy volunteers (part A)
1) Male and 18-65 years old at screening.
2) Able and willing to comply with study procedures, with signed and dated
informed consent obtained before any study-related procedures are performed.
3) Agree to use an effective method of contraception for 90 days after
administration.
4) A body mass index is *30 kg/m2.
5) The subject is healthy with no acute or chronic medical illnesses, has a
normal physical examination, and normal vital signs findings at screening.
6) The subject*s screening 12-lead ECG and clinical laboratory test results are
within normal limits, or if any are outside of normal limits they are
considered clinically insignificant at the discretion of the investigator.
7) Negative screening test results for hepatitis B, hepatitis C, and human
immunodeficiency virus.
8) Negative test results for drug and alcohol screening.
9) Absence of any psychological, familial, sociological or geographical
condition that at the discretion of the investigator could potentially hamper
compliance with the study protocol and follow-up schedule; such conditions
should be discussed with the patient during the prescreening period.
Patients (part B)
1) Male patients > 18 years of age and older at screening.
2) Able and willing to comply with study procedures, and signed and dated
informed consent obtained before any study-related procedures are performed.
3) Known or high clinical suspicion of (primary or recurrent) prostate cancer
scheduled to undergo a pelvic lymph node dissection for salvage or staging at
the LUMC.
4) The 12-lead ECG and clinical laboratory test results are within normal
limits, or if any are outside of normal limits they are considered clinically
insignificant at the discretion of the investigator
5) Chronic or acute medical illness that in the discretion of the investigator
may confound or complicate the findings in this study
6) Patients are clinically fit for surgery
7) Agree to use an effective method of contraception for 90 days after
administration
8) Absence of psychological familial, sociological or geographical condition
that at the discretion of the investigator could potentially hamper compliance
with the study protocol and follow- up schedule; such conditions should be
discussed with the patient during the prescreening period.
Patients (part C)
1) Male patients > 18 years of age and older at screening.
2) Able and willing to comply with study procedures, and signed and dated
informed consent obtained before any study-related procedures are performed.
3) Known or high clinical suspicion of prostate cancer (Gleason score 7+)
planned for a prostatectomy at the NKI.
4) The 12-lead ECG and clinical laboratory test results are within normal
limits, or if any are outside of normal limits they are considered clinically
insignificant at the discretion of the investigator
5) Chronic or acute medical illness that in the discretion of the investigator
may confound or complicate the findings in this study
Protocol Version 1.5 / 17-Jan-2020 Page 22 of 68
6) Patients are clinically fit for surgery
7) Agree to use an effective method of contraception for 90 days after
administration
8) Absence of psychological familial, sociological or geographical condition
that at the discretion of the investigator could potentially hamper compliance
with the study protocol and follow- up schedule; such conditions should be
discussed with the patient during the prescreening period.
Exclusion criteria
Healthy volunteers (part A)
1) Female subjects
2) Known acute or chronic disease, abnormal physical examination or blood tests
of clinical significance.
3) The subject has previously been included in an OTL study.
4) Use of prescription drugs within 30 days of screening and during study
participation
5) Participation in a clinical trial within 90 days of screening or more than 4
times in the previous year.
6) History of clinically significant allergies or anaphylactic reactions.
7) History of allergy to any of the components of OTL78 or excipients (see
Investigator*s Brochure).
Patients (part B)
1) Any condition that in the opinion of the investigators could potentially
jeopardize the health status of the patient
2) History of clinically significant allergies or anaphylactic reactions
3) History of allergy to any of the components of OTL78 or excipients (see
Investigator*s Brochure)
4) Impaired renal function defined as eGFR<50 ml/min/1.73m2
5) Impaired liver function defined as values greater than 3x the upper limit of
normal (ULN) for ALT, AST, or 2x the upper limit of normal for total bilirubin
(excl. Gilbert*s syndrome)
6) Previous participation in an OTL study
Patients (part C)
1) Any condition that in the opinion of the investigators could potentially
jeopardize the health status of the patient
2) History of clinically significant allergies or anaphylactic reactions
3) History of allergy to any of the components of OTL78 or excipients (see
Investigator*s Brochure)
4) Impaired renal function defined as eGFR<50 ml/min/1.73m2
5) Impaired liver function defined as values greater than 3x the upper limit of
normal (ULN) for ALT, AST, or 2x the upper limit of normal for total bilirubin
(excl. Gilbert*s syndrome)
6) Previous participation in an OTL study
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 | EUCTR2019-002393-31-NL |
| CCMO | NL70379.056.19 |
| OMON | NL-OMON21822 |