PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: 177LU-PSMA-617
Product Code: 177LU-PSMA-617
Pharmaceutical Form: Solution for injection
INN or Proposed INN: 177LU-PSMA-617
Other descriptive name: 177LU-PSMA-617
Concentration unit: GBq
Sponsors
Endocyte, Inc., a Novartis company
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Patients must have the ability to understand and sign an approved ICF. 2. Patients must have the ability to understand and comply with all protocol requirements. 3. Patients must be =18 years of age. 4. Patients must have an ECOG performance status of 0 to 2. 5. Patients must have a life expectancy >6 months. 6. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer. 7. Patients must have a poitive 68Ga-PSMA-11 PET/CT scan as determined by the sponsor’s central reader. 8. Patients must have a castrate level of serum/plasma testosterone (3.0 g/dL (3.0 g/dL is equivalent to 30 g/L) 16. Patients on a stable bisphosphonate or denosumab regimen for =30 days prior to randomization are eligible. 17. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. For patients who have partners of childbearing potential: 18. Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principle investigator during the stu
Exclusion criteria
Exclusion criteria: 1. Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed. 2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to day of randomization. 3. Any investigational agents within 28 days prior to day of randomization. 4. Known hypersensitivity to the components of the study therapy or its analogs. 5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy. 6. Transfusion for the sole purpose of making a subject eligible for study inclusion. 7. Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast). 8. A superscan as seen in the baseline bone scan. 9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. 10. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. 11. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients with a prior history of malignancy that has been adequately treated and who have been disease free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, superficial bladder cancer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the two alternate primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/standard of care versus patients treated by best supportive/best standard of care alone.;Secondary Objective: Key secondary objectives are an arm-to-arm comparison of the following: 1. RECIST response to include: a. Overall Response Rate (ORR) as measured by RECIST v1.1 criteria b. Disease control rate (DCR) as measured by RECIST v1.1 criteria 2. Time to a first symptomatic skeletal event (SSE) Additional secondary objectives 1. Safety and tolerability of 177Lu-PSMA-617 2. Periodic assessment of health-related quality of life to evaluate impact of intervention on patient well-being (HRQoL; EuroQol 5-dimensions 5-level [EQ-5D-5L] questionnaire, Functional Assessment of Cancer Therapy – Prostate [FACT-P] questionnaire and Brief Pain Inventory – Short Form [BPI-SF]) 3. Health Economics 4. Progression-free survival (PFS) (radiographic, clinical, or PSA progression-free survival) 5. Biochemical response as measured by PSA. Alkaline phosphatase [ALP] and lactate dehydrogenase [LDH] levels will also be collected. 6. Dosimetry, PK, and ECG in a sub-study of approximately 30 patients;Primary end point(s): rPFS and OS are designated as alternate primary endpoints. rPFS is defined as the time from the date of randomization to the date of radiographic disease progression as outlined in Prostate Cancer Working Group 3 (PCWG3) Guidelines (Scher et al 2016) or death from any cause. OS is defined as the time from randomization to the date of death from any cause.;Timepoint(s) of evaluation of this end point: for rPFS: Every 8 weeks (± 4 days) after first dose of 177Lu-PSMA-617 for the first 24 weeks (independent of dose delays), then every 12 weeks (± 4 days) For OS: Continuously during study treatme | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Continuously during study, except ORR and PSA response, which are evaluated per Prostate Cancer Working Group 3 criteria. ORR and PSA response evaluated every 3 months during long term follow-up. Dosimetry will be collected during every Cycle, PK and ECG will be collected during the first week of Cycle 1 ;Secondary end point(s): The key secondary endpoints include the following: 1. RECIST response to include: a. Objective response rate (ORR) (CR + PR) as measured by RECIST v1.1 response in soft tissue, lymph node and visceral lesions. Duration of Response will also be measured in patients with a CR or PR from date of first response to the date of RECIST progression or death. b. Disease Control Rate (DCR) (CR + PR + stable disease [SD]) as measured by RECIST v1.1 response in soft tissue, lymph node and visceral lesions. 2. The time to a first SSE defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first. Additional Secondary endpoints 1. To evaluate the safety and tolerability of 177Lu-PSMA-617 2. Aspects of HRQoL will be reported using the EuroQol 5-dimensions 5-level [EQ-5D-5L] questionnaire, Functional Assessment of Cancer Therapy – Prostate [FACT-P] questionnaire and Brief Pain Inventory – Short Form [BPI-SF] 3. Health economics 4. Progression-free survival is defined as the date of randomization to the date of first evidence of radiographic progression, clinical progression, PSA progression, or death from any cause, whichever occurs first. a. Radiographic progression is defined as the date of radiographic disease progression as outlined in the Prostate Cancer Working Group 3 (PCWG3) Guidelines. b. Unequivocal clinical progression. Unequivocal evidence of clinical progression is defined as: • Marked escal | — |
Countries
Belgium, Canada, Denmark, France, Germany, Netherlands, Sweden, United Kingdom, United States
Contacts
Public ContactVISION Study Team
Endocyte, Inc., a Novartis company
Outcome results
None listed