Metastatic Castration-Resistant Prostate Cancer, Prostate Cancer, Prostate Cancer (CRPC), Prostate Cancer Metastatic, Prostate Cancer Patients With Bone Metastasis
Conditions
Keywords
Metastatic Castration-Resistant Prostate Cancer (mCRPC), super scan bone scan, Prostate Cancer patients with bone metastasis, prostate cancer (CRPC), Prostate cancer, Prostate cancer metastatic
Brief summary
The purpose of this study is to evaluate the safety and tolerability of Lutetium-177-PSMA-617 (PLUVICTO) in patients with metastatic castration-resistant prostate cancer (mCRPC) and extensive bone metastases, which appear as a super scan pattern on a bone scan. Pluvicto is FDA-approved, but patients with super scan bone scans were previously excluded from the VISION clinical trial, leaving a knowledge gap. The study will enroll up to 30 men with metastatic castration-resistant prostate cancer, with an initial dosing approach that differs from the standard dose. The safety and tolerability of PLUVICTO will be evaluated in this study, with a focus on identifying the optimal dose for this population. This study addresses an important gap in understanding how Pluvicto performs in mCRPC patients with super scan findings.
Detailed description
This clinical study investigates the safety and effectiveness of the FDA-approved drug Pluvicto (Lu-177-PSMA617). It focuses on a unique group of patients with metastatic castration-resistant prostate cancer (mCRPC) who present with a super scan on bone scintigraphy-a pattern indicating widespread cancer in the bones. These patients were excluded from prior trials like the VISION study, leaving a critical gap in clinical understanding. The trial aims to identify the optimal safe dose of Pluvicto using a modified 3+3 dose-escalation method, beginning at a low dose that increases, and eventually reaching up to 200 mCi. Participants will receive a total of six doses, spaced every 6 ± 1 weeks. Primary objectives include determining the maximum tolerated dose and monitoring safety using CTCAE version 5.0 criteria. Efficacy will be evaluated through PSA level reductions based on PCWG3 guidelines. Secondary endpoints include quality of life, radiologic response (RECIST v1.1), and overall survival. Exploratory endpoints involve PSMA PET/CT imaging to measure treatment response through SUVmean and lesion changes. The study includes up to 30 participants and will include expanded enrollment once the optimal dose is determined. Routine lab tests (CBC, CMP, PSA, testosterone) and patient-reported side effects will be monitored throughout the study. Long-term follow-up for survival and safety will continue every six months for up to five years. Imaging (CT/MRI, bone scans, and optional PET/CT) will be performed at baseline, mid-treatment, end of treatment, and every three months post-treatment. A complete or partial response, stable disease, or progression will be defined using both RECIST and PCWG3 guidelines. Monthly PSA checks will continue for up to 24 months or until disease progression. PLUVICTO is administered via IV infusion over 2-5 minutes during each session. Participants may discontinue due to progression, intolerable side effects, non-compliance, or other clinical decisions. This study is essential in determining how to safely extend Pluvicto therapy to a previously unstudied and high-risk patient group. Its results may expand access to this radioligand therapy and guide future treatment decisions in prostate cancer care.
Interventions
DRUGAdministering Lutetium-177-PSMA-617 (PLUVICTO)
The study begins with a first cohort of three participants, each receiving a dose of 100 millicuries (mCi). After administration, participants are monitored for any dose-limiting toxicities (DLTs) during a predefined observation window. If fewer than two participants experience a DLT in a given cohort, the dose will be escalated for the next group. The dose escalation schedule is structured as follows: the second cohort receives 130 mCi (a 30% increase), the third cohort receives 162.5 mCi (a 25% increase), and the fourth cohort receives 200 mCi, a dose that is already FDA-approved and clinically accepted for mCRPC. This stepwise escalation continues until the 200 mCi dose is reached, or until two or more DLTs are observed in any cohort. If that occurs, escalation stops immediately, and the maximum tolerated dose is considered to be the previous lower dose. This becomes the optimal tolerated dose (OTD). After identifying the OTD, additional participants will be enrolled for treatment.
Sponsors
Ebrahim S Delpassand
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study uses an FDA-approved drug (PLUVICTO). Therefore, it is not subject to phase categorization.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to understand and sign an informed consent form (ICF). 2. Willingness and ability to comply with study requirements. 3. Age ≥18 years. 4. Presence of skeletal metastases with a superscan pattern on a 99mTc-MDP/HDP bone scan, defined by significantly increased skeletal radioisotope uptake relative to soft tissues and faint or absent renal activity. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 6. Hemoglobin ≥9.0 g/dL. 7. Platelet count ≥90 × 10⁹/L. 8. White blood cell count ≥2.0 × 10⁹/L, absolute neutrophil count (ANC) \>1.5 × 10⁹/L. o These hematologic criteria must be met without recent transfusions (within 28 days prior to the first study treatment) or growth factor support (within 21 days). 9. Serum/plasma creatinine ≤1.5 × upper limit of normal (ULN). 10. Histological, pathological, or cytological confirmation of prostate cancer. 11. Positive PSMA PET/CT scan showing at least one PSMA-positive metastatic lesion. 12. Castrate-level serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L). 13. Prior treatment with at least one androgen receptor-axis-targeted therapy (ARAT).
Exclusion criteria
1. Prior treatment with radiopharmaceuticals (e.g., Strontium-89, Samarium-153, Rhenium- 186, Rhenium-188, Radium-223, hemi-body irradiation) within six months before start of treatment under this protocol. 2. Prior PSMA-targeted radioligand therapy. 3. Systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, monoclonal antibodies) within four weeks before screening visit. 4. Known hypersensitivity to PLUVICTO or its components. 5. Concurrent treatment with other cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy. 6. Renal impairment (estimated glomerular filtration rate \<60 mL/min), hemoglobin \<9 g/dL, ANC \<1.5 × 10⁹/L, or platelets \< 90 × 10⁹/L. 7. History of CNS metastases unless treated and stable for 6 months, with no ongoing corticosteroid use. 8. Symptomatic or impending spinal cord compression. 9. Other malignancies impacting life expectancy or interfering with study assessments. Exceptions include non-melanoma skin cancer or superficial bladder cancer that has been adequately treated. 10. Major surgery within 30 days prior to enrollment. 11. Plans to conceive or father a child during treatment and up to six months post-treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic progression-free survival | From date of enrollment until the date of first documented radiographic disease progression or date of death from any cause, whichever came first, assessed up to 24 months. | rPFS: Defined as the time from enrollment to radiographic disease progression, based on Prostate Cancer Working Group 3 (PCWG3) Guidelines (Scher et al., 2016), or death from any cause. |
| Overall Survival | From date of enrollment until the date of death from any cause, assessed up to 24 months. | OS: Defined as the time from enrollment to death from any cause. |
Countries
United States
Contacts
Primary ContactSusan Cork Therapy Coordinator
Backup ContactNereyda Sauceda, Therapy Coordinator
Outcome results
None listed