NCT05458544

[Lu-177]Ludotadipep in Castration-resistant Prostate Cancer(CRPC): Investigation of Drug and Application

A Phase 1 Open-label, Dose-finding Multi-center Trial of [177Lu]Ludotadipep in Metastatic Castration-resistant Prostate Cancer Patients, Followed by an Open-label, Repeat Dose, Multi-center Phase 2a Trial to Assess Safety and Efficacy

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: FutureChem · Industry
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase 1: The objective of the Phase 1 part of the clinical trial is to verify safety and tolerability (dose-limiting toxicity \[DLT\], maximum tolerated dose \[MTD\]) of a single 3.7 Giga-Becquerel (GBq) dose with the potential for one dose level de-escalation to 2.775 GBq if necessary, to determine the recommended \[177Lu\]Ludotadipep dose for use in the Phase 2a part of the trial. Phase 2a: The objective of the Phase 2a part of the trial is to evaluate safety and efficacy for repeated administration of the recommended \[177Lu\]Ludotadipep dose. The Recommended Phase 2 dose (RP2D) will be based on the study results from the Phase 1 trial in South Korea upon consultation with the FDA.

Detailed description

Phase 1: The patient will attend a Screening visit (-28 to -1 days) prior to study treatment, where it will be determined if the patient is eligible to, and consents to, participate in the trial based on the inclusion/exclusion criteria. \[Ga-68\]PSMA-11 positron emission tomography (PET)/CT scan will be performed at screening. Patients who are finally registered for trial participation will be injected with a single dose of \[177Lu\]Ludotadipep. Ice packs and other cooling therapies will be applied to the major salivary glands from 30 minutes before the administration of \[177Lu\]Ludotadipep to 60 minutes after the administration to prevent side effects such as sialadenitis. Amino acid solution will be administered slowly intravenously for renal protection over approximately 4 hours from 30 minutes before treatment to 3.5 hours after treatment. 500 mL of 0.9% sodium chloride (NaCl) will be administered slowly intravenously for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment. Adverse events and DLTs will be assessed continuously for the duration of the 8 \[±1\] week study period. Other measurements, corresponding to secondary outcomes, are detailed in the Schedule of Assessments and include concomitant medications, laboratory tests, physical examination, vital signs, Eastern cooperative oncology group performance status (ECOG PS), imaging (positron emission tomography-computed tomography \[PET/CT\], bone scan and Whole Body Scan (WBS)). Follow-up will occur at scheduled visits 1, 2, 4 and 8 weeks after investigational product (IP) administration. Patients who show a clinical response and who the PI considers will likely benefit from retreatment can be so treated after consultation and agreement of the medical monitor and the sponsor. Phase 2a: The patient will attend a Screening visit (-28 to -1 days) prior to treatment with IP, where it will be determined if the patient is eligible to, and consents to, participate in the trial based on the inclusion/exclusion criteria. \[Ga-68\]PSMA-11 PET/CT and \[F-18\]FDG-PET scans will be performed at screening. Patients who are finally registered for trial participation will be injected with a single dose of \[177Lu\]Ludotadipep. Ice packs and other cooling therapies will be applied to the major salivary glands 30 minutes before and up to 60 minutes after the administration of \[177Lu\]Ludotadipep to prevent side effects such as sialadenitis. Amino acid solution will be administered slowly intravenously for renal protection over approximately 4 hours from 30 minutes before treatment to 3.5 hours after treatment. 500 mL of 0.9% NaCl will be administered slowly intravenously for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment. WBS or single photon emission computed tomography (SPECT) images will be obtained 24 hours after each administration and Day 7, and AE information will also be captured. Other measurements are detailed in the Schedule of Assessments. Patients will receive \[177Lu\]Ludotadipep every 8 \[±1\] weeks (4 to 6 times). Patients will be contacted by phone 2 weeks after the first administration for a safety check-up. Four and six weeks after each administration the patient will attend the clinic for a follow-up visit. The following assessments will be performed: * PSA and other laboratory blood tests (4 and 6 weeks) * AEs (4 and 6 weeks) * Urinalysis, physical examination, vital signs, ECOG PS, EORTC QLQ-C30 and Pain Response questionnaires (4 weeks only) The decision on whether to proceed with additional administrations will be determined every 6 weeks after administration of the IP, based on investigator's assessment of tolerability. If a patient does not progress to the next dose administration at 8 weeks, a PSA blood sample will be taken. A tumor response assessment by CT and bone scan, and additional \[Ga-68\]PSMA-11 PET/CT and FDG-PET scans will be conducted at end of treatment (EOT). All follow up assessments are detailed in the Schedule of Assessments. All patients will have long term follow-up every 6 months for 2 years after the last dose of IP unless there is death, withdrawal of consent, or loss to follow-up. Patients who are alive at \>2 years after the last dose of IP, unless there is death, withdrawal of consent, or loss to follow-up will be offered participation in a long-term follow-up protocol for up to 10 years. In the long-term survival follow-up, the long-term outcome of the known serious risk of myelosuppression, renal failure, xerostomia, xerophthalmia, and their complications; the potential serious signals of secondary malignancies including myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML); and other serious adverse reactions, will be monitored.

Conditions

• Metastatic Castration-resistant Prostate Cancer

Interventions

Type	Name	Description
DRUG	[177Lu]Ludotadipep 3.7 GBq	Phase 1: Patients will receive a single dose of 3.7 GBq of \[177Lu\]Ludotadipep * Test article code/name: \[177Lu\]Ludotadipep * Administration route: intravenous injection * Total dose strength: 3.7 GBq * Dosage form: solution for injection Phase 2a: Patients will receive 3.7 GBq of \[177Lu\]Ludotadipep every 8 \[±1\] weeks (4 to 6 times) * Test article code/name: \[177Lu\]Ludotadipep * Administration route: intravenous injection * Total dose strength: 4 to 6 x 3.7 GBq * Dosage form: solution for injection

Timeline

• Start date: 2022-09-01
• Primary completion: 2025-06-01
• Completion: 2025-06-01
• First posted: 2022-07-14
• Last updated: 2024-04-29

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study