Trial Title:
Targeted Radionuclide Therapy in Metastatic Prostate Cancer Using a New PSMA Ligand Radiolabelled With Terbium-161 (161Tb-SibuDAB) - Dose Identification/Escalation Phase Ia/b Study
NCT ID:
NCT06343038
Condition:
Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Conditions: Keywords:
Radioligand Therapy
Phase Ia/Ib
Circulating Tumour Cells
Biomarkers Development
Voxel-based 3D Dosimetry
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Intervention model description:
In Phase Ia:
Radiation dosimetry driven, head-to-head in cross-over design comparison of tumour and
critical organ absorbed doses after sequential non-therapeutic injections of
161Tb-SibuDAB and 177Lu-PSMA-I&T in the same mCRPC patients undergoing standard
177Lu-PSMA-I&T RLT.
In Phase Ib:
Clinical and radiation dosimetry-based dose escalation study, with a classical 3+3
design, to identify the optimal biologic dose (injected activity) of 161Tb-SibuDAB for
safe and effective RLT.
Primary purpose:
Treatment
Masking:
Single (Participant)
Intervention:
Intervention type:
Drug
Intervention name:
Injection, 161Tb-SibuDAB,1GBq
Description:
Intravenous injection via peripheral venous catheter of ~1GBq 161Tb-SibuDAB (~200 μg /
~125 nM) in saline
Arm group label:
Cross-Over Group A
Arm group label:
Cross-Over Group B
Intervention type:
Drug
Intervention name:
Injection, 177Lu-PSMA-I&T, 1GBq
Description:
Intravenous injection via peripheral venous catheter of ~1GBq 161Tb-SibuDAB (~100 μg /
~65 nM) in saline
Arm group label:
Cross-Over Group A
Arm group label:
Cross-Over Group B
Intervention type:
Drug
Intervention name:
Injection, 161Tb-SibuDAB, Dose Escalation
Description:
Intravenous injection via peripheral venous catheter of 161Tb-SibuDAB in saline. The
intervention comprises 4 cycles at 6-week intervals.
The 161Tb-SibuDAB entry activity will be calculated based on dosimetry and toxicity data
from the first 3 patients in Phase Ia of the study.
The escalated or de-escalated 161Tb-SibuDAB activity for the subsequent 3-patient cohorts
will be determined based on the clinical and biochemical safety information and on organ
dosimetry results of the entry/previous cohort. Up to 4 escalation or de-escalation steps
will be performed.
Arm group label:
Dose Escalation Study
Summary:
Researchers will test a new treatment for prostate cancer. This treatment uses an
antibody tagged with a small amount of radioactive material. Researchers believe the new
antibody might work better than those used before.
In the first part of the study researchers will compare the new treatment to the old one
on prostate cancer patients using very low doses, not strong enough to treat nor to cause
strong adverse reactions. Each patient will eventually receive both treatments, but one
at a time.
The aim of the second part of the study is to find the best dose of the new treatment for
patients. This means finding the dose that offers the most benefits with the fewest side
effects.
The performance of different prostate cancer diagnostic methods is also in scope of the
study.
Detailed description:
Radioligand therapy (RLT) has emerged as an effective treatment of metastatic, castration
resistant prostate cancer (mCRPC) for those patients having, prostate-specific membrane
antigen (PSMA)-positive disease. This led to the FDA approval of 177Lu-PSMA-617
(PluvictoTM), a PSMA ligand radiolabelled with the β--particle emitter
lutetium-177(177Lu). Despite the success of this treatment modality, the therapeutic
response after RLT with 177Lu-based PSMA radioligands is limited and disease relapse
inevitable. In addition, approximately 1/3 of the patients does not respond to
177Lu-based RLT despite PSMA-positive mCRPC.
It has been hypothesized that the insufficient absorbed dose delivery to macroscopic
tumours and, in particular, to microscopic metastases with currently used 177Lu-based
PSMA radioligands is the reason for the treatment failure in these patients. SibuDAB, a
novel long-circulating PSMA ligand, was successfully tested in the preclinical setting in
combination with terbium-161 (161Tb) that emits not only β--particles but also conversion
and Auger electrons and, hence, delivers 2-4 times higher absorbed doses to microscopic
tumours than 177Lu.
The researchers, therefore, propose to enhance the efficacy of PSMA-targeting RLT by
using the long-circulating ligand (SibuDAB) labelled with 161Tb. The researchers expect
161Tb-SibuDAB to exhibit increased and/or prolonged tumour uptake with a higher
deposition of energy (due to short ranged Auger electrons) resulting in a high linear
energy transfer (LET) and, hence, relative biological effectiveness. 161Tb-SibuDAB should
not only deliver the absorbed dose to the cellular nucleus (via β-- radiation) but also
to the cell membrane and organelles (through the emission of conversion and Auger
electrons) which, in mathematical models, leads to a 3-4-fold increased absorbed dose to
single cancer cells compared to standard RLT.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Consent form signed
- Male patients with age > 18 years
- Clinical indication for RLT with 177Lu-PSMA-I&T (progressive PSMA-positive mCRPC
patients after androgen receptor signalling pathway inhibitor and taxan-based
chemotherapy or patient unfit for chemotherapy)
- Patients will be included in Phase Ia while being under active therapy with
177Lu-PSMA-I&T (SoC) and after they have completed the first two cycles of
177Lu-PSMA-I&T RLT
- At least 3 measurable tumours on PSMA PET/CT (>1.5 cm) with sufficiently intense
PSMA uptake (SUVmax>20)
- ECOG Performance status: 0-1
- Blood parameters: a) Leucocytes ≥ 3 G/L; b) Haemoglobin ≥ 100 g/L; c) Thrombocytes ≥
100 G/L
- Estimated glomerular filtration rate (eGFR) > 45 ml/min
- Albumin > 25 g/L
- ALT, AST, AP: ≤ 5 times upper standard value
- Bilirubin ≤ 2 times upper standard value
- For male patients who are not surgically sterilized (orchiectomy or vasectomy),
appropriate contraceptive measures must be taken during RLT and until 4 months after
completion of RLT. As acceptable contraceptive count sexual abstinence or double
contraceptive methods: hormonal contraceptive (oral, transdermal, implants or
injections) in combination with barrier methods (spiral, condom, diaphragm)
Exclusion Criteria:
- Prior PSMA-targeted RLT (except for the 2 first cycles in Part Ia)
- PSMA-negative (or PSMA-negative / FDG-positive) disease
- Known intolerance against DOTA, DOTAGA, urea-based analogues or against any of the
components/formulation of 177Lu-PSMA-I&T or 161Tb-SibuDAB solutions.
- Ongoing infection at the screening visit or a serious infection in the past 4 weeks
- Administration of another investigational product in the last 60 days before Visit 1
Day 1
- Prior or planed administration of a therapeutic radiopharmaceutical during 8
half-lives of the used radio-pharmaceutical's radionuclide, also during the ongoing
study
- Any extensive radiotherapy involving bone marrow over the last 3 months before
inclusion to the study
- Chemotherapy in the last 4 weeks before inclusion
- Any uncontrolled significant medical, psychiatric or surgical condition (active
infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled
hypertension, poorly controlled diabetes mellitus [HbA1c ≥ 9%], uncontrolled
congestive heart disease, etc.) or laboratory findings that might jeopardize the
patient's safety or that would limit compliance with the objectives and assessments
of the study. Any mental conditions which prevent the patient from understanding the
type, extent and possible consequences of the study and/or an uncooperative attitude
from the patient.
- Current history of any malignancy other than prostate cancer within 5 years of
enrolment except for fully resected non-melanoma skin cancer
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital Basel
Address:
City:
Basel
Zip:
4031
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Alin Chirindel, MD
Phone:
+41 61 328 63 75
Email:
alin.chirindel@usb.ch
Contact backup:
Last name:
Guillaume Nicolas, MD
Phone:
+41 61 265 47 02
Email:
guillaume.nicolas@usb.ch
Start date:
February 20, 2024
Completion date:
June 2028
Lead sponsor:
Agency:
University Hospital, Basel, Switzerland
Agency class:
Other
Source:
University Hospital, Basel, Switzerland
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06343038
