Clinical Trials in Italy / NCT06004661
Active, not recruiting
Phase 2
Study of Lutetium (177Lu) Vipivotide Tetraxetan in mCRPC Participants With Moderately and Severely Impaired and With Normal Renal Function
NCT06004661 · tracked via the Priya Life Science Italy tracker
Condition(s) studied
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Investigational drug(s) / intervention(s)
AAA617: Administered intravenously once every cycles (1 cycle = 6 weeks)
68Ga-PSMA-11: Single intravenous dose of approximately 150 MBq
Study 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.
Eligibility
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 chronic renal disease without evidence of further deterioration in renal function (stable chronic renal disease is defined as no significant change in renal function 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/1.73m2
* Moderate renal impairment: participants with eGFR \>= 30 to =\< 59 mL/min/1.73m2
* Severe renal impairment: participants with eGFR \>= 15 to =\< 29 mL/min/1.73m2
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 prostatectomy) 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 (12 lead ECG) \<60 bpm
Other protocol-defined inclusion/exclusion criteria may apply.
Primary outcome measure(s)
- Absorbed radiation dose in kidneys and selected organs — Up to 36 weeks
The absorbed dose in kidneys and selected organs will be summarized with descriptive statistics. - Concentrations of AAA617 in blood over time — Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Blood concentration of \[177Lu\]Lu-PSMA-617 will be summarized with descriptive statistics. - Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 177Lu-PSMA-617 — Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics. - Time of maximum observed drug concentration occurrence (Tmax) of 177Lu-PSMA-617 — Cycle (C) 1 Day (D) 1 (2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle = 6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics. - Observed maximum plasma concentration (Cmax) of 177Lu-PSMA-617 — Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics. - Terminal elimination half-life (T^1/2) of 177Lu-PSMA-617 — Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics - Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 177Lu-PSMA-617 — Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics. - Total systemic clearance for intravenous administration (CL) of 177Lu-PSMA-617 — Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics. - Volume of distribution during the terminal phase following intravenous elimination (Vz) of 177Lu-PSMA-617 — Cycle (C) 1 Day (D) 1 (pre dose, end of infusion, 20 minutes (min), 60 min, 2 and 4 hours (h) post infusion), C1 D2 (24 h post infusion), C1 D3 (48 h post infusion), C1 D4 (72 h post infusion), C1 D6 (120-144 h post infusion). Cycle=6 weeks
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics. - Change from baseline in eGFR — at screening and at every visit, assessed up to 1 year after last treatment
Change from baseline of eGFR will be summarized for each post-dose (post-baseline) timepoint. The summary includes table with descriptive statistics at baseline, post-baseline time points and change from baseline to post-baseline timepoints. - Dose modifications for AAA617 — Up to 36 weeks
Dose modifications (dose interruptions and reductions) for AAA617 will be assessed and summarized using descriptive statistics. - Dose intensity for AAA617 — Up to 36 weeks
Dose intensity for AAA617 will be assessed and summarized using descriptive statistics.
Trial sites (9)
| Facility | City | Region | Status |
|---|---|---|---|
| Mount Sinai Hosp Med School | New York | New York | |
| Novartis Investigative Site | Paris | France | |
| Novartis Investigative Site | Vandœuvre-lès-Nancy | France | |
| Novartis Investigative Site | Essen | Germany | |
| Novartis Investigative Site | München | Germany | |
| Novartis Investigative Site | Milan | Italy | |
| Novartis Investigative Site | Naples | Italy | |
| Novartis Investigative Site | Granada | Andalusia | |
| Novartis Investigative Site | El Palmar | Murcia |
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Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT06004661 on ClinicalTrials.gov ↗ ← All trials in Italy