This study has been transitioned to CTIS with ID 2024-513729-22-01 check the CTIS register for the current data. 1.1 Primary study objectives To investigate the safety, tolerability and biochemical effects of 225Ac-PSMA injected in patients with…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study endpoints
· Safety and tolerability of 225Ac-PSMA in patients with mCRPC as assessed by:
o Incidence and severity of adverse events and serious adverse events
o Absolute values and changes from baseline in laboratory parameters
(hematology, blood chemistry and urinalysis), including assessment of shifts
from baseline to abnormal values on treatment
o Absolute values and changes from baseline in vital signs & ECG parameters
Secondary outcome
Secondary study endpoints
· The following 68Ga-PSMA distribution and radiation dosimetry endpoints will
be calculated:
o Volume calculations of critical organs and tumor by PET-MRI.
o Expected radiotracer uptake calculated as a percentage of the injected dose
per gram of tissue (%ID/g)
o Expected absorbed doses and effective whole body dose of 225Ac-PSMA
· Direct effect of 225Ac-PSMA will be monitored by:
o Changes in SUVmax of the target lesions on PET-MRI
o Changes in perfusion measured on MRI
· The preliminary action of the therapeutic doses of 225Ac-PSMA will be
assessed according to the last PET-MRI. These imaging techniques will be used
to derive the following endpoints where relevant:
o Objective response rate (ORR) as measured by RECIST criteria v.1.1. This is
defined as the number of patients with either a complete response (CR) or
partial response (PR) at any time point which is confirmed a minimum of 4 weeks
later, divided by the total number of patients with visceral disease at
baseline.
o Percent changes from baseline in tumor size where tumor size is defined as
the sum of all target lesions as measured by RECIST 1.1. Only patients with
measurable disease at baseline (i.e. target lesions identified and measured)
will contribute to these analyses.
o PSA response rate assessed from treatment visit 1 defined as a decrease in
PSA of >= 50% from baseline.
o Percent change from baseline in PSA as a continuous endpoint by visit and
maximum reduction during the study
o Percent change from baseline values of pain questionnaire at every treatment
visit
o Overall Survival defined as the time from the date of first dose of
225Ac-PSMA treatment to the date of death due to any cause. Any subject not
known to have died at the time of the analysis will be censored based on the
last recorded date on which the subject was known to be alive.
Background summary
PSMA is a type II transmembrane glycoprotein with a domain both intracellular
and extracellular. PSMA is expressed on benign prostate epithelium and on
prostate cancer cells. There is also expression of PSMA in other tissues such
as the kidneys, small intestine and the salivary glands. However, the
expression on prostate cancer cells is a thousand-fold higher than expression
on normal tissues and therefore a target for both imaging and therapy of
prostate cancer. PSMA has a large extracellular domain and specific inhibitors
can internalize after binding to the receptor. Imaging with Gallium-68 or
Fluor-18 labeled PSMA-ligands is now widely used for primary staging of
prostate cancer, but also for detection of recurrent disease in patient with a
biochemical recurrence. In the recent years different PSMA-ligands were
developed for imaging and therapy. In the Netherlands, the most frequently used
tracer for imaging is 68Ga-PSMA-11. For therapy, both PSMA-617 and PSMA I&T are
used. With the use of PSMA I&T, the same ligand can be used for imaging and
therapy when labeled to different radionuclides.
Study objective
This study has been transitioned to CTIS with ID 2024-513729-22-01 check the CTIS register for the current data.
1.1 Primary study objectives
To investigate the safety, tolerability and biochemical effects of 225Ac-PSMA
injected in patients with metastatic prostate cancer.
Primary objective:
- To assess the safety and tolerability of 225Ac-PSMA administered intravenously
Secondary study objectives
Secondary objectives:
- To predict and calculate the absorbed-dose in critical organs (e.g. salivary
glands, kidneys, bone marrow) by 68Ga-PSMA PET/MRI
- To evaluate the effects of the radionuclide therapy on metastases in the days
after therapy using 68Ga-PSMA PET/MRI
- To evaluate the biochemical effects of 225Ac-PSMA therapy
Study design
A clinical prospective, single-center, single-arm, phase I dose escalation
therapy study.
Intervention
Ac-PSMA
Study burden and risks
Participation in this study requires additional blood draws, imaging, infusion
of the IMP, hospitalization and follow-up visits.
Total needed blood volume varies between 30-80 ml per blood draw. Blood draws
will take place before each cycle and during follow-up visits. Additionally,
blood will be drawn direct after infusion of the IMP and then over time (in
total 13 times) to measure the radioactivity of the tracer and its daughters in
blood, which is necessary for good dosimetry. The risk of blood being drawn is
minimal.
Patients will undergo additionally three times imaging with PET-MRI, two times
with SPECT/CT and five times with a gamma-camera during the study. From
protocol version 3 patients will undergo additionally three times imaging with
PET-MRI, one time with SPECT/CT and three times with a gamma-camera during the
study. Scans for dosimetry will add an extra radiation dose of 2,5 mSV from the
low-dose CT to the patients. Considering the age of the patients, the prognosis
and the potential benefit of this study for future treatment of prostate cancer
patients, the radiation burden of the protocol is considered justified.
Due to the Dutch safety regulations regarding dose limitations for hospital
discharge, all patients should be hospitalized during one night after each
treatment. From literature, it is not expected that patients will have acute
side-effects from the IMP infusion. Expected side-effect will be subacute,
therefore follow-up visits are necessary to monitor each patient close.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
- Histopathological proven metastatic castration resistant prostate cancer
- Progression after at least one line of chemotherapy and one line of
nonsteroidal antiandrogen
Exclusion criteria
- Concurrent severe illness or clinically relevant trauma within 2 weeks before
the administration of the investigational product that might preclude study
completion or interfere with study results
- Serum hemoglobin <= 6.2 mmol/L, total white blood cell (WBC) count <= 2·109/L,
platelet count <= 100·109/L, serum creatinine concentration >= 150 umol/L (>= 1.7
mg/dL), serum albumin <30 g/L
- Concurrent bladder outflow obstruction or unmanageable urinary incontinence
- Known or expected hypersensitivity to Gallium-68, Actinium-225, PSMA, or any
excipient present in 225Ac/68Ga-PSMA
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 |
|---|---|
| EU-CTR | CTIS2024-513729-22-01 |
| EudraCT | EUCTR2020-001089-13-NL |
| CCMO | NL73234.078.20 |