Lutetium treatment for prostate cancer patients with varying kidney function

An Open-label Dosimetry, Biodistribution, Tolerability and Safety Study of Lutetium (177Lu) Vipivotide Tetraxetan in Participants With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Moderately and Severely Impaired and With Normal Renal Function.

This study is testing a new treatment for prostate cancer to see how safe it is for patients with different levels of kidney function.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 100 Years
• Sex: Male
• Sponsor: Novartis (industry)
• Drugs / interventions: radiation
• Locations: 9 sites (New York, New York and 8 other locations)
• Trial ID: NCT06004661 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the safety and tolerability of lutetium (177Lu) vipivotide tetraxetan in patients with metastatic castration-resistant prostate cancer (mCRPC) who have moderate to severe renal impairment, compared to those with normal renal function. Participants will be stratified into three cohorts based on their kidney function and will receive treatment every six weeks for a planned number of cycles. The study aims to assess the impact of renal function on the biodistribution and safety of the treatment, as well as monitor potential QT prolongation risks. A long-term follow-up will be conducted to ensure ongoing safety monitoring for up to ten years post-treatment.

Who should consider this trial

Good fit: Ideal candidates include men diagnosed with progressive PSMA-positive mCRPC who have varying degrees of renal function.

Not a fit: Patients with normal renal function or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for mCRPC patients with renal impairment, improving their outcomes.

How similar studies have performed: While this approach is novel in its focus on renal impairment in mCRPC, similar studies have shown promise in targeting PSMA-positive cancers.

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 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.

Where this trial is running

New York, New York and 8 other locations

• Mount Sinai Hosp Med School — New York, New York, United States (RECRUITING)
• Novartis Investigative Site — Paris, France (RECRUITING)
• Novartis Investigative Site — Vandœuvre-lès-Nancy, France (RECRUITING)
• Novartis Investigative Site — Essen, Germany (RECRUITING)
• Novartis Investigative Site — München, Germany (RECRUITING)
• Novartis Investigative Site — Milan, Italy (RECRUITING)
• Novartis Investigative Site — Naples, Italy (RECRUITING)
• Novartis Investigative Site — Granada, Andalusia, Spain (RECRUITING)
• Novartis Investigative Site — El Palmar, Murcia, Spain (ACTIVE_NOT_RECRUITING)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions: Metastatic Castration-Resistant Prostate Cancer, Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer, Prostate-specific membrane antigen, PSMA, mCRPC, Renal impairment, Moderately impaired renal function, Severely impaired renal function