A Study of Radiation Dosimetry, Safety, and Tolerability of Extended Lutetium (177Lu) Vipivotide Tetraxetan Treatment in Chemo-naïve Adults With Metastatic Castration-resistant Prostate Cancer: RADIOpharmaceutical DOSimetry Evaluation (RADIODOSE) Study

NCT06531499 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CAAA617A121012024-512338-13
• Study Type: interventional
• Target: 106
• Locations: 6 countries
• Sites: 21

Brief Summary

The purpose of the study is to assess and evaluate dosimetry, safety, and tolerability following administration of up to 12 cycles of (177Lu) vipivotide tetraxetan (also referred to as \[177Lu\]Lu-PSMA-617 or 177Lu-PSMA-617 and hereafter identified as AAA617) in taxane-naïve adult participants with PSMA-positive mCRPC who progressed on a prior ARPI treatment with normal renal function or mild renal impairment (eGFR ≥ 60ml/min).

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

Phase 1; RADIODOSE; AAA617; metastatic castration-resistant prostate cancer; radiation dosimetry; mCRPC; Prostate-specific membrane antigen (PSMA); Dosimetry; [68Ga]Ga-PSMA-11; gallium (68Ga) gozetotide; [177Lu]Lu-PSMA-617; lutetium (177Lu) vipivotide tetraxetan; Radioligand Imaging (RLI); Radioligand Therapy (RLT)

Outcome Measures

Primary Outcomes (3)

• Time activity curves (TACs) and absorbed radiation dose of AAA617 in organs

  Time activity curve (TAC) will be generated from the amount radioactivity in one given tissue. Time integrated activity coefficient and absorbed dose will be calculated

  From Cycle 1 to Cycle 12; cycle = 42 days

• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  The distribution of adverse events for Radioligand Therapy (RLT) will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters. Adverse event monitoring should be continued for at least 42 days following the end of treatment (EOT) visit. Participants receiving the study treatment will continue to be followed for safety every 12 weeks during the long-term follow-up for selected adverse events

  For up to 12 cycles in taxane-naive participants with progressive PSMA-positive mCRPC with nrmal kidney function or mild renal impairment; cycle = 42 days

• Percentage of participants with AAA617 dose reductions, interruptions and discontinuations

  The assessment of tolerability will be based on the frequency of participants with dose interruptions, reductions, and study treatment discontinuations. Dose reduction will be based on the worst toxicity demonstrated at the last dose.

  Up to 42 (+7) days after last AAA617 dose administration (Safety Follow-up)

Secondary Outcomes (15)

• Time activity curves (TACs) and absorbed radiation dose AAA617 in tumors

  For up to 12 cycles; cycle = 42 days

• Pharmacokinetic ( PK) concentration of AAA617 in blood over time

  Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12, cycle = 42 days

• Pharmacokinetic (PK) parameter Cmax of AAA617 from blood radioactivity data

  Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

• PK parameter Tmax of AAA617 from blood radioactivity data

  Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

• PK parameter AUC of AAA617 from blood radioactivity data

  Cycle 1, Cycle 4, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11 and Cycle 12; cycle = 42 days

Study Arms (1)

AAA617

EXPERIMENTAL

All participants will receive the investigational product AAA617 (7.4 GBq ±10%).

Drug: AAA617; Drug: Gonadotropin-releasing hormone (GnRH) analogues; Drug: Gonadotropin-releasing hormone (GnRH) antagonists

Interventions

AAA617 DRUG

\[177Lu\]Lu-PSMA-617 will be administered as an intravenous infusion at a dose of 7.4 GBq (200mCi) (+/- 10%), every 6 weeks for up to 12 cycles.

Also known as: Lutetium (177Lu) vipivotide tetraxetan, [177Lu]Lu-PSMA-617

AAA617

Gonadotropin-releasing hormone (GnRH) analogues DRUG

Anatomical Therapeutic Chemical \[ATC\] code L02AE

AAA617

Gonadotropin-releasing hormone (GnRH) antagonists DRUG

Degarelix, Relugolix

AAA617

Eligibility Criteria

• Age: 18 Years - 100 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study.
• Participants must be adults ≥ 18 years of age.
• Participants must have an ECOG performance status ≤ 1.
• Participants must have histological confirmation of adenocarcinoma of the prostate.
• Participants must be PSMA-positive per 68Ga-PSMA PET/CT scans at baseline
• Participants must have a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L) either by pharmaceutical or surgical methods.
• Participants must have progressed only once on prior second generation ARPIs
• Documented progressive mCRPC
• Participants must have ≥ 1 metastatic lesion by conventional imaging that is present on screening/baseline CT, MRI, or bone scan
• Renal: eGFR ≥ 60 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• Participants must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies except alopecia.

You may not qualify if:

• Previous treatment with any of the following within 6 months of study enrollment: Strontium 89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
• Any previous radioligand therapy.
• Prior treatment with cytotoxic chemotherapy for metastatic castration-resistant or metastatic hormone-sensitive prostate cancer (mHSPC) (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy \[including monoclonal antibodies\]. \[Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy. Prior treatment with sipuleucel-T is allowed\].
• Concurrent therapies: cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological, or investigational therapy
• History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
• Concurrent serious acute or chronic nephropathy and/or moderate to severe renal impairment as determined by the principal investigator.
• Diagnosed with other active malignancies that are expected to alter life expectancy or may interfere with disease assessment
• Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment.
• Concurrent urinary outflow obstruction or unmanageable urinary incontinence
• History of somatic or psychiatric disease/condition that may interfere with the aims and assessments of the study.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

University of California LA

Los Angeles, California, 90095, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Wash U School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

Novartis Investigative Site

Wuppertal, North Rhine-Westphalia, 42283, Germany

RECRUITING

Novartis Investigative Site

Aachen, 52074, Germany

RECRUITING

Novartis Investigative Site

Berlin, 13353, Germany

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

München, 80377, Germany

RECRUITING

Novartis Investigative Site

Rostock, 18057, Germany

RECRUITING

Novartis Investigative Site

Nijmegen, Gelderland, 6500HB, Netherlands

RECRUITING

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

RECRUITING

Novartis Investigative Site

Majadahonda, Madrid, 28222, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08041, Spain

RECRUITING

Novartis Investigative Site

Bellinzona, 6500, Switzerland

RECRUITING

Novartis Investigative Site

Bern, 3010, Switzerland

RECRUITING

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

Novartis Investigative Site

Birmingham, West Midlands, B15 2TH, United Kingdom

RECRUITING

Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

RECRUITING

MeSH Terms

Interventions

Lutetium; Lutetium-177; Gonadotropin-Releasing Hormone

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Transition Elements; Metals; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be assigned to a treatment arm based on their PSMA expressed target per PET images (based on central read).

Study Record Dates

• First Submitted: June 18, 2024
• First Posted: August 1, 2024
• Study Start: November 11, 2024
• Primary Completion (Estimated): November 24, 2028
• Study Completion (Estimated): November 24, 2028
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); GB (3); NL (1); DE (7); US (5); CH (2)