A Phase I Study of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer
Purpose
The main purpose of the study is to assess the safety and tolerability of AZD2284, AZD2287, and AZD2275.
Condition
- Metastatic Castration-Resistant Prostate Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. - Histologically confirmed diagnosis of adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer. - Must have had prior bilateral orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L). - At least one metastatic lesion present on baseline Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or bone scan obtained ≤ 28 days prior to the first dose of Investigational Medicinal Product (IMP). Participants may have non-measurable lesions including bone only metastases. - Adequate organ function Main
Exclusion Criteria
- Treatment with any radiopharmaceutical within 6 weeks of the first dose of Investigational Medicinal Product (IMP). - Radiation therapy (RT) within 28 days prior to the first dose and all RT-related events have not recovered to Grade ≤ 1. - Administration of any systemic cytotoxic or investigational therapy ≤ 28 days of the first dose of IMP or 5 half-lives, whichever is shorter. - All prior treatment-related adverse events must have resolved to Grade ≤ 1. - Concurrent severe and/or uncontrolled illness not related to cancer and/or social situation that would limit compliance with study requirements. - Known or suspected allergies or contraindications to any of the investigational drugs or any component of the investigational drug formulation. - Clinically relevant proteinuria
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part A: Cohort A1: AZD2287 (Hot only) |
Participants will receive 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. |
|
|
Experimental Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot) |
Participants will receive low dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. |
|
|
Experimental Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot) |
Participants will receive medium dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284. |
|
|
Experimental Part A Expansion: AZD2287 + AZD2275 (Cold + Hot) |
Participants will receive dose of AZD2275 determined earlier in the study followed by 1 dose of AZD2287. |
|
|
Experimental Part B (Actinium-225 Dose Escalation): low dose: AZD2284 |
Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive low dose of AZD2284. |
|
|
Experimental Part B (Actinium-225 Dose Escalation): medium dose: AZD2284 |
Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive medium dose of AZD2284. |
|
|
Experimental Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284 |
Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. |
|
|
Experimental Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284 |
Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284. |
|
|
Experimental Part B: Cohort E1 |
Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level. |
|
|
Experimental Part B: Cohort E2 |
Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level. |
|
Recruiting Locations
Research Site
Miami, Florida 33165
Miami, Florida 33165
Research Site
Omaha, Nebraska 68130
Omaha, Nebraska 68130
More Details
- NCT ID
- NCT06879041
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
information.center@astrazeneca.com
Detailed Description
This is a first-in-human, Phase I, non-randomized, open-label clinical trial designed to evaluate AZD2284, AZD2287, and AZD2275. This trial will consist of 2 Parts: Part A (Imaging): - Part A (Cold Antibody Exploration): aims to determine the optimal dosing regimen, with or without unconjugated antibody (AZD2275) pre-administration to improve the biodistribution of AZD2287. - Part A Expansion: aims to explore the prevalence of PSMA and STEAP2 expression by imaging. Part B (Therapeutic): - Part B (Actinium-225 Dose Escalation): aims to assess the safety, tolerability, and efficacy of escalating doses of AZD2284 informed by the optimal dosing regimen identified in Part A. - Part B Expansion Cohorts 1 and 2: aims to explore efficacy of AZD2284.