In this proposed study, we aim to test not only the safety and biodistribution of [68Ga]Sarabesin 3, but also its potential to visualise prostate cancer. If the peptide proves to be successful, a next study will be initiated to test the potential to…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objectives
- to assess the safety of 275 MBq [68Ga]Sarabesin 3 (40 µg peptide) in patients
with PC;
= endpoints: adverse events (AE), with severity grading according to NCI
CTCAE version 4.0; the causality of each AE to [68Ga]Sarabesin 3;
= outcome measures: blood pressure, heart rate, haemoglobin, leucocytes,
thrombocytes, CRP, sodium, potassium, calcium, phosphate, urea, creatinine,
total protein, albumin, bilirubin, alkaline phosphatase, ALT, AST, gamma-GT,
uric acid, glucose, and gastrin;
- to determine the biodistribution of [68Ga]Sarabesin 3 in patients with PC;
= endpoint: biodistribution of [68Ga]Sarabesin 3 will be assessed by PET;
= outcome measures: qualitative and quantitative data per region of interest
per patient within the available time points;
Secondary outcome
Secondary objectives
- to evaluate the pharmacokinetics of [68Ga]Sarabesin 3 in patients with PC;
= endpoint: pharmacokinetic assessment of [68Ga]Sarabesin 3 in blood and if
achievable in urine;
= outcome measures: determination of degradation products, in plasma 5, 10,
30 and 60 minutes p.i. and urine samples 30 and 60 minutes p.i., time activity
curve in blood from 5 min to 180 min p.i.; activity measurement in urine in 4
time frames: 0-30, 30-60, 60-90, 90-180 min p.i.;
- to assess the potential of [68Ga]Sarabesin 3 to visualise tumour lesions in
patients with biopsy-proven PC that is assumed to be confined to the primary
organ;
= endpoint: visualisation of primary carcinoma.
= outcome measures: imaging judged by two experienced nuclear physicians.
- to compare imaging results with receptor expression estimated on tissue
samples in vitro;
= endpoint: correlation of visibility of prostate cancer lesions by imaging
(visual grading and if achievable quantitative) with GRPr density by
autoradiography;
= outcome measures: in consensus scored scans; SUVmax of tumour lesions;
GRPr density in DLU/mm2 on tumour tissue;
- to compare histological results with receptor expression estimated on tissue
samples in vitro;
= endpoint: correlation of results of histological evaluation performed by
the pathologist with GRPr density by autoradiography;
= outcome measures: Gleason score, size of lesion, GRPr density in DLU/mm2
on tumour tissue.
Background summary
Crucial for the design of the optimal treatment schedules of prostate cancer
patients is accurate staging of the disease. If the tumour is still confined to
the prostate, curative treatment - surgical removal or local radiotherapy - is
the best choice. However, these therapies can lead to severe adverse effects
like erectile or urinary tract dysfunction and should only be offered to
patients who are treated with a curative intent. Besides the need for accurate
staging at presentation of the disease, a sensitive diagnostic technique is
needed to detect local relapse or metastatic disease of prostate cancer in
patients with rising PSA after local therapy. In almost 95 % of cases the
rising PSA is the only indication for relapse: physical examination, CT, bone
scan, and other routinely used imaging procedures are usually negative. A
sensitive imaging method might visualize tumour tissue more accurately and
thereby improve patient management.
Study objective
In this proposed study, we aim to test not only the safety and biodistribution
of [68Ga]Sarabesin 3, but also its potential to visualise prostate cancer. If
the peptide proves to be successful, a next study will be initiated to test the
potential to visualise lymphe node and distant metastases in patients with more
advanced disease.
Study design
The study is a single-centre, non-randomized, non-therapeutic, phase I study of
radiolabelled Sarabesin 3 given in a single intravenous bolus for the imaging
of PC. In this phase I study the focus lies on safety, biodistribution, and
pharmacokinetics of the radiopeptide and its potential to visualise proven
primary prostate cancer lesions.
Study burden and risks
The patient will have to come extra to the hospital for one day for study
purposes. The whole study procedure will take about 5 hours, during which the
patient will be scanned several times. Whenever possible regular pauses are
included in the protocol. The follow-up for the study will be performed in
combination with routine clinical follow-up visits(after prostatectomy).
There are some very low risks associated with placement, presence, and removal
of venflons and the urine catheter. The risks of administrating the
investigational product are prevented by working according to Good
Manufacturing Practice. The product will only be administered if it passes all
quality controls listed in the IMPD. Biological effects caused by the compound
are not expected as this is a receptor antagonist and the amount of peptide is
very small. In a pilot study in Bad Berka, Germany (see below) a similar dose
was used without any side effects.
No data concerning dosimetry of [68Ga]Sarabesin 3 are published yet. The
estimated mean dose of the proposed imaging protocol is 11.8 mSv.
Direct benefits for the patients included in this study are not expected since
only patients without suspicion of metastases are selected. In the unexpected
case of suspicion of metastases on the images, the urologist will decide how to
use this information.
One of the aims of this study is to explore the potential of [68Ga]Sarabesin 3
imaging in prostate cancer patients. If the peptide proves promising, it might
help to more accurately stage PC by detecting metastases in (other) PC
patients. Improved staging of individual patients suffering from PC will result
in optimized care.
Patients scheduled for prostatectomy are required, because a comparison will be
made between imaging results, histopathology, and in vitro autoradiography of
GRPr density.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
- male patients of 18 years and older;
- histologically confirmed prostate cancer, no clinical suspicion of
metastasis;
- patient is scheduled for radical prostatectomy;
- capable of cooperating with imaging procedure and follow-up;
- World Health Organisation (WHO) performance status 0-2;
- signed and dated informed consent.
Exclusion criteria
- current severe and/or uncontrolled and/or unstable other medical
disease (e.g. poorly controlled diabetes, unstable and uncontrolled
hypertension, chronic renal or hepatic disease, severe pulmonary
disease);
- other known malignancies (except local skin cancer);
- chemotherapy, radiotherapy, or anti-hormonal therapy prior to study;
- 5-alpha-reductase inhibitors prior to study;
- significant cardiac arrhythmia current or in patient history;
- prior NYHA (New York Heart Association) class III-IV cardiac disease
or concurrent congestive heart failure;
- prior major thoracic and/or abdominal surgery from which the patient
has not yet recovered;
- known sensitivity to the study drug or components of the preparation;
- other concurrent investigational drugs within the past four weeks;
- other condition that, in the opinion of the investigators, would make
the patient unsuitable for this clinical trial.
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 | EUCTR2011-005859-13-NL |
| CCMO | NL38643.078.13 |