Treatment for advanced prostate cancer using a targeted radiopharmaceutical

[Ac-225]-PSMA-62 Phase I/II Clinical Trial to Characterize Efficacy, Safety, Tolerability, and Dosimetry in Oligometastatic Hormone Sensitive and Metastatic Castration Resistant Prostate Cancer (ACCEL)

This study is testing a targeted radiation treatment for advanced prostate cancer to see how safe and effective it is for patients with specific types of the disease.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 142 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Eli Lilly and Company (industry)
• Drugs / interventions: chemotherapy, radiation
• Locations: 7 sites (Vancouver, British Columbia and 6 other locations)
• Trial ID: NCT06229366 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of [Ac-225]-PSMA-62, a targeted radiopharmaceutical, in patients with prostate cancer that expresses prostate-specific membrane antigen (PSMA). The study is divided into three phases: the first phase assesses the maximum tolerated dose, the second phase optimizes the dose for patients with metastatic castration-resistant prostate cancer (mCRPC) and oligometastatic hormone-sensitive prostate cancer (OmHSPC), and the third phase evaluates the treatment's effectiveness in mCRPC patients. Participants will be monitored for safety and treatment response throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include men with confirmed adenocarcinoma of the prostate who have progressed after standard therapies and have a performance status of 0 to 1.

Not a fit: Patients who have not received prior androgen receptor pathway inhibitors or taxane-based chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new targeted therapy option for patients with advanced prostate cancer, potentially improving outcomes and quality of life.

How similar studies have performed: Other studies using targeted radiopharmaceuticals for prostate cancer have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate
2. ECOG performance status 0 to 1
3. Criteria specific for patients with mCRPC:

   1. 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
   2. 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
   3. At least one PSMA-PET positive lesion for prostate cancer
   4. Castrate circulating testosterone levels (\<1.74 nmol/L or \<50 ng/dL)
4. Criteria specific for patients with OmHSPC:

   1. 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
   2. 1- 5 PSMA-PET positive lesions identified outside the prostate bed or remaining gland.

Exclusion Criteria:

1. Patient has received any other investigational therapeutic agents within 4 weeks or 5 half-lives (whichever is shorter) of starting the study treatment
2. Evidence of ongoing and untreated urinary tract obstruction
3. Existing Grade 1 dry mouth (xerostomia) or symptomatic Grade 1 dry eye (xerophthalmia) for any reason
4. 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
5. Criteria specific for patients with mCRPC:

   1. Patient has received any PSMA-directed radioligand therapy (e.g., Lu-177-PSMA, Lu-177-PNT2002, Ac-225-J591)
   2. 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
6. Criteria specific for patients with OmHSPC:

   1. Patient has received any systemic anti-cancer therapy for prostate cancer with the exception of (neo)adjuvant ADT for management of localized disease
   2. Presence of any liver metastases
   3. Known presence of central nervous system metastases

Where this trial is running

Vancouver, British Columbia and 6 other locations

• BC Cancer Vancouver — Vancouver, British Columbia, Canada (RECRUITING)
• Juravinski — Hamilton, Ontario, Canada (NOT_YET_RECRUITING)
• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (RECRUITING)
• Jewish General Hospital — Montreal, Quebec, Canada (NOT_YET_RECRUITING)
• McGill University — Montreal, Quebec, Canada (RECRUITING)
• Hopital De Chicoutimi — Saguenay, Quebec, Canada (NOT_YET_RECRUITING)
• Centre Hospitalier Universite de QUEBEC — Quebec, Canada (RECRUITING)

Study contacts

• Study coordinator: Richard Cioci

Conditions: Prostate Cancer, Metastatic Castration-resistant Prostate Cancer, Oligometastatic Prostate Carcinoma, Hormone Sensitive Prostate Cancer, mCRPC, OmHSPC, Prostatic Neoplasms, Genital Neoplasms, Male