[Ac-225]-PSMA-62 Trial in Oligometastatic Hormone Sensitive and Metastatic Castration Resistant Prostate Cancer

NCT06229366 | Active Not Recruiting Phase 1

• 2 other identifiers: 27197J5N-OX-JJEA
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 7

Brief Summary

ACCEL is a multicenter, open label phase Ia/Ib/II study of \[Ac-225\]-PSMA-62 in participants with prostate-specific membrane antigen (PSMA)-positive prostate cancer.

Conditions

Oligometastatic Prostate Carcinoma; Hormone Sensitive Prostate Cancer; Prostate Cancer; Metastatic Castration-resistant Prostate Cancer

Keywords

mCRPC; OmHSPC; Prostatic Neoplasms; Genital Neoplasms, Male; Castration Resistant Prostate Cancer; Hormone Sensitive Prostate Cancer; Oligometastatic Prostate Cancer; [225Ac]-PSMA-62; Ac-225-PSMA-62; Actinium; Radioligand Therapy; Radiopharmaceuticals; Urogenital Neoplasm

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  Phase Ia: Incidence of dose limiting toxicities (DLTs)

  From first dose of study drug through end of DLT period (4 weeks)

• Safety, tolerability, and Recommended Phase II Dose (RP2D)

  Phase 1b: Incidence and severity of treatment emergent adverse events (TEAEs)

  From first dose of study drug through end of treatment (~16 - 24 weeks)

• Safety and tolerability

  Phase Ia: Incidence and severity of treatment emergent adverse events (TEAEs)

  From first dose of study drug through end of treatment (~16 - 24 weeks)

Secondary Outcomes (8)

• The incidence of treatment emergent adverse events as assessed per CTCAE v5.0

  From first dose of study drug through end of study (~5 years)

• Time to initiation of any life-long ADT, or other systemic hormonal therapies for prostate cancer

  From first dose of study drug through end of study (~5 years)

• Absorbed dose estimates (Gy) in normal organs

  From first dose of study drug through end of treatment (~16 - 24 weeks)

• The proportion of patients with a PSA change from baseline

  From first dose of study drug through efficacy follow-up period (up to approximately 3 years)

• Objective Response Rate (ORR)

  From first dose of study drug until disease progression (up to approximately 3 years)

Study Arms (2)

OmHSPC

EXPERIMENTAL

Patients with prostate cancer and biochemical recurrence after definitive surgery or radiation therapy, with 1-5 PSMA-positive lesions, who have not yet initiated lifelong hormone therapy.

Drug: [Ac-225]-PSMA-62 (OmHSPC)

mCRPC

EXPERIMENTAL

Patients with PSMA-positive mCRPC who have prior treatment with at least one APRI and received taxane chemotherapy (or ineligible/refused); and received a maximum of 3 prior systemic therapy regimens in the mCRPC setting.

Drug: [Ac-225]-PSMA-62 (mCRPC)

Interventions

[Ac-225]-PSMA-62 (OmHSPC) DRUG

Phase Ia: Administered intravenously per dose escalation scheme. Patients will receive a single dose of \[Ac-225\]-PSMA-62 on Day 1 of each 8-week cycle for up to 2 cycles. Phase Ib: Administered intravenously at MTD or one dose level below MTD. Patients will receive a single dose of \[Ac-225\]-PSMA-62 on Day 1 of each 8-week cycle, for a total of 2 cycles.

OmHSPC

[Ac-225]-PSMA-62 (mCRPC) DRUG

Phase Ia: Administered intravenously per dose escalation scheme. Patients will receive a single dose of \[Ac-225\]-PSMA-62 on Day 1 of each 6-week cycle for up to 4 cycles. Phase Ib: Administered intravenously at MTD or one dose level below MTD. Patients will receive a single dose of \[Ac-225\]-PSMA-62 on Day 1 of each 6-week or 4-week cycle, for a total of 4 cycles.

mCRPC

Eligibility Criteria

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

You may qualify if:

• Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate
• ECOG performance status 0 to 1
• Criteria specific for patients with mCRPC:
• Previously received an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy (unless ineligible or refused taxane). Received a maximum of 3 prior systemic therapy regimens in the mCRPC setting
• Progressive mCRPC at the time of consent based on at least 1 of the following criteria being met in the context of castrate levels of testosterone:
• PSA progression defined as rising PSA values at a minimum of 1-week intervals, with the last result being at least 1.0 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 defined as the appearance of two or more new lesions by bone scan
• At least one PSMA-PET positive lesion for prostate cancer
• Castrate circulating testosterone levels (\<1.74 nmol/L or \<50 ng/dL)
• Criteria specific for patients with OmHSPC:
• PSA recurrence after radical prostatectomy (RP) or definitive radiation therapy (RT), with or without adjuvant/salvage local therapy (radiation or surgery), with or without (neo)adjuvant ADT
• PSA ≥ 0.2ng/mL for patients with prior RP +/- RT, or
• PSA of ≥ 2 ng/mL above nadir for patients with only prior RT
• PSMA-PET positive lesions identified outside the prostate bed or remaining gland.

You may not qualify if:

• Patient has received any other investigational therapeutic agents within 4 weeks or 5 half-lives (whichever is shorter) of starting the study treatment
• Evidence of ongoing and untreated urinary tract obstruction
• Existing Grade 1 dry mouth (xerostomia) or symptomatic Grade 1 dry eye (xerophthalmia) for any reason
• Patient has any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while on the study or that could confound discrimination between disease- and study treatment-related toxicities
• Criteria specific for patients with mCRPC:
• Patient has received any PSMA-directed radioligand therapy (e.g., Lu-177-PSMA, Lu-177-PNT2002, Ac-225-J591)
• Patient has received any therapeutic systemic radionuclides (e.g., radium-223, rhenium-186, strontium-89), or non-PSMA-directed therapeutic radioligands (e.g., Lu-177-Dotatate) within 5 half-lives of starting the study treatment
• Criteria specific for patients with OmHSPC:
• Patient has received any systemic anti-cancer therapy for prostate cancer with the exception of (neo)adjuvant ADT for management of localized disease
• Presence of any liver metastases
• Known presence of central nervous system metastases

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (7)

Juravinski

Hamilton, L8V 5C2, Canada

Location

Jewish General Hospital

Montreal, H3T 1E2, Canada

Location

McGill University

Montreal, H4A 3J1, Canada

Location

Centre Hospitalier Universite de QUEBEC

Québec, G1J 1Z4, Canada

Location

Hopital De Chicoutimi

Saguenay, G7H 5H6, Canada

Location

Princess Margaret Cancer Centre

Toronto, M5G 2M9, Canada

Location

BC Cancer Vancouver

Vancouver, V5Z4E6, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: January 29, 2024
• Study Start: April 3, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2032
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

CA (7)