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Trial Title:
Study of Lutetium (177Lu) Vipivotide Tetraxetan in mCRPC Participants With Moderately and Severely Impaired and With Normal Renal Function
NCT ID:
NCT06004661
Condition:
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Conditions: Official terms:
Prostatic Neoplasms
Gallium 68 PSMA-11
Conditions: Keywords:
Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer
Prostate-specific membrane antigen
PSMA
Metastatic Castration-Resistant Prostate Cancer
mCRPC
Renal impairment
Moderately impaired renal function
Severely impaired renal function
Normal renal function
lutetium (177Lu) vipivotide tetraxetan
AAA617
Dosimetry
QTc prolongation
post marketing requirement
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Participants confirmed for enrollment in IRT will be stratified in one of the three
cohorts based on eGFR calculated (MDRD formula) at screening:
- Cohort A: normal renal function eGFR >= 90 mL/min,
- Cohort B: moderate renal impairment eGFR >= 30 to =< 59 mL/min
- Cohort C: severe renal impairment eGFR >= 15 to =< 29 mL/min.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AAA617
Description:
Administered intravenously once every cycles (1 cycle = 6 weeks)
Arm group label:
AAA617
Other name:
Pluvicto
Other name:
177Lu-Lu-PSMA-617
Intervention type:
Drug
Intervention name:
68Ga-PSMA-11
Description:
Single intravenous dose of approximately 150 MBq
Arm group label:
AAA617
Summary:
This study will address health authorities' requests to determine whether moderate and
severe renal impairment have an impact on the biodistribution, dosimetry and safety of
lutetium (177Lu) vipivotide tetraxetan (AAA617) administered to participants with
progressive PSMA-positive metastatic castration-resistant prostate cancer. The study will
also characterize the risk of QT prolongation of AAA617 in this participant population.
Detailed description:
This open-label, non-randomized, multicenter, single arm phase II study in mCRPC
participants aims to better characterize the safety and tolerability of AAA617 in
participants with moderate and severe renal impairment compared with normal renal
function. Since both severe and moderate renal impairment have very low incidence within
mCRPC participant population compared to participants with normal renal function, the
enrollment will occur in parallel for the 3 cohorts; participants will be stratified in
one of the three cohorts (A:normal, B: moderate or C: severe) based on their eGFR at
screening.
All participants will undergo a 68Ga-PSMA-11 PET/CT scan at screening to confirm PSMA
positivity.
Participants will receive a dose of 7.4 GBq (±10%) of AAA617 once every 6 weeks for a
planned 6 cycles for cohorts A and B and for 3 cycles (and 3 additional cycles) for
cohort C.
After treatment period, participants will be asked to join a long term follow up (LTFU)
study to monitor their safety up to 10 years after the 1st dose of AAA617. In case of the
LTFU study is not available at the time of end of treatment period (safety follow-up
visit), participants will continue in Long Term Follow-up period in this study for up to
one year until they can roll over into the separate LTFU study.
The primary outcome will be to determine the effect of radiation absorption in kidney and
other organs at risk as well as the concentration in blood and radioactivity in urine in
PSMA- positive mCRPC participants with moderate and severe renal impairment. In addition,
the study will assess the relationship between drug concentrations and QTcF.
20 participants with 6 countries are expected to be included with at least 6 evaluable
participantts per cohort.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
1. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
2. 68Ga-PSMA-11 Positron emission tomography (PET)/CT scan positive, and eligible as
determined by the sponsor's central reader.
3. A castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
4. Documented progressive mCRPC will be based on at least 1 of the following criteria:
- Serum/plasma Prostate-Specific Antigen (PSA) progression defined as 2
consecutive increases in PSA over a previous reference value measured at least
1 week prior. The minimal start value is 2.0 ng/mL
- Soft-tissue progression defined as an increase >= 20% in the sum of the
diameter (SOD) (short axis for nodal lesions and long axis for non-nodal
lesions) of all target lesions based on the smallest SOD since treatment
started or the appearance of one or more new lesions.
- Progression of bone disease: evaluable disease or new bone lesions(s) by bone
scan (2+2 PCWG3 criteria)
5. Documented stable renal disease without evidence of renal progressive disease
(stable renal disease is defined as no significant change, such as a stable eGFR,
within 4 weeks prior to study entry)
6. Kidney function based on eGFR by Modification of Diet in Renal Disease (MDRD)
equation:
- Normal renal function: participants with eGFR >= 90 mL/min
- Moderate renal impairment: participants with eGFR >= 30 to =< 59 mL/min
- Severe renal impairment: participants with eGFR >= 15 to =< 29 mL/min
Key Exclusion Criteria:
1. Previous treatment with PSMA-targeted radioligand therapy.
2. Previous treatment with any of the following within 6 months of enrollment
confirmation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or
hemi-body irradiation.
3. Use of agents known to prolong the QT interval from start of screening to end of
Cycle 1, unless they can be permanently discontinued for the duration of study.
4. Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any
level of urinary obstruction requiring indwelling/condom catheters. Participants
with postrenal impairment, like obstructions, retroperitoneal fibrosis (eg after
prostectomy) must be excluded or first resolved to ≤ Grade 1.
5. History or current diagnosis of ECG abnormalities indicating significant risk of
safety for participants participating in the study such as:
- Concomitant clinically significant cardiac arrhythmias, e.g. sustained
ventricular tachycardia, and clinically significant second- or third-degree AV
block without a pacemaker.
- History of familial long QT syndrome or known family history of Torsades de
Pointe.
- Resting heart rate (physical exam or 12 lead ECG) <60 bpm
Other protocol-defined inclusion/exclusion criteria may apply.
Gender:
Male
Gender based:
Yes
Gender description:
Prostate cancer
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Novartis Investigative Site
Address:
City:
Paris
Zip:
75014
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Vandoeuvre Les Nancy
Zip:
54511
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Muenchen
Zip:
80377
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Milano
Zip:
20141
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Granada
Zip:
18014
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
El Palmar
Zip:
30120
Country:
Spain
Status:
Recruiting
Start date:
April 4, 2024
Completion date:
July 29, 2026
Lead sponsor:
Agency:
Novartis Pharmaceuticals
Agency class:
Industry
Source:
Novartis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06004661
