PSMA-positive metastatic castration-resistant prostate cancer MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study 2. Participants must be adults = 18 years of age 3. Participants must have an ECOG performance status of 0 to 1 4. Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate 5. Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader 6. Participants must have a castrate level of serum/plasma testosterone (=65 years) yes F.1.3.1 Number of subjects for this age range 315
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 2. Previous PSMA-targeted radioligand therapy 3a. Prior treatment with cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy [including monoclonal antibodies]. [Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy. Prior treatment with sipuleucel-T is allowed.] 4. Any investigational agents within 28 days prior to day of randomization 5. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes 6a. Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological, or investigational therapy 7. Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for study inclusion 8a. Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. 9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression 10. History or current diagnosis of the following ECG abnormalities indicating significant risk of safety for study participants: • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block) • History of familial long QT syndrome or known family history of Torsades de Pointe •Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or CABG within 6 months prior to starting study treatment Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the trial is to evaluate whether treatment with 177LuPSMA-617 improves the time to radiographic progression by PCWG3- modified RECIST v1.1 or death in participants with progressive PSMA-positive mCRPC compared to participants treated with ARDT ;Secondary Objective: Key Secondary Objective is to evaluate whether treatment with 177LuPSMA-617 improves the overall survival (OS) in participants with progressive PSMA-positive mCRPC compared to participants treated with ARDT treatment Secondary objectives are : - To evaluate Progression free survival (PFS) by investigator's assessment - To evaluate the second progression Free Survival (PFS2) by investigator's assessment - To evaluate whether treatment with 177LuPSMA-617 improves the biochemical response as detected by Prostate specific antigen (PSA)having compared to participants treated with ARDT - To evaluate whether treatment with 177LuPSMA-617 improves the time to first symptomatic skeletal event (TTSE) compared to participants treated with ARDT - To evaluate whether treatment with 177LuPSMA-617 improves the time to radiographic soft tissue progression compared to participants treated with ARDT other protocol-defined secondary objectives may apply. ;Primary end point(s): Radiographic progression-free survival (rPFS) is designated as primary end point. rPFS is defined as the time from the date of randomization to the date of first documented radiographic disease progression as assessed by blinded independent central review (BICR) and as outlined in Prostate Cancer Working Group 3 (PCWG3) Guidelines (Scher et al 2016) or death due to any cause;Timepoint(s) of evaluation of this end point: Every 8 weeks after first dose of study treatment for the first 24 weeks (week 8, 16, 24) and then every 12 weeks (week 36, 48, etc) until confirmation of radiographic progression by BICR | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS) is designated as key secondary endpoint of the trial. (OS) is defined as time from randomization to death due to any cause Secondary end points are the following: - rPFS2 defined as time from the date of crossover (ARDT to 177Lu-PSMA-617) to the date of radiographic disease progression by BICR or death from any cause [rPFS definition as outlined in PCWG3 guidelines] - PFS defined as time from date of randomization to the first documented progression by investigator's assessment (radiographic, clinical, or PSA progression) or death from any cause, whichever occurs first - PFS2 defined as time from date of randomization to the first documented progression by investigator's assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first, on next-line of therapy - PSA50 defined as proportion of participants who achieved a = 50% decrease from baseline that is confirmed by a second PSA measurement = 4 weeks. PSA50 will be evaluated at 3, 6 and 12 months. - Time to SSE (TTSSE) 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 - Time to soft tissue progression (TTSTP) defined as time from randomization to radiographic soft tissue progression per PCWG3-modified RECIST v1.1 (Soft Tissue Rules of Prostate Cancer Working Group modified Response Evaluation Criteria in Solid Tumors Version 1.1) as Assessed by Blinded Independent Central Review (BICR) - Time to chemotherapy (TTCT) defined as time from randomization to initiation of the first subsequent chemotherapy or death, whichever occurs first - HRQoL as assessed by EQ-5D-5L, FACT-P and BPISF - Frequency of adverse events, safety laboratory assessments and vital signs ;Timepoint(s) of evaluation of | — |
Countries
Austria, Belgium, Canada, Czechia, Czech Republic, France, Germany, Netherlands, Poland, Slovakia, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed