177Lu-PSMA-617 vs. Androgen Receptor-directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer (PSMAfore)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04689828 |
Recruitment Status :
Active, not recruiting
First Posted : December 30, 2020
Last Update Posted : March 20, 2024
|
Tracking Information | |||||||
---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | December 9, 2020 | ||||||
First Posted Date ICMJE | December 30, 2020 | ||||||
Last Update Posted Date | March 20, 2024 | ||||||
Actual Study Start Date ICMJE | June 15, 2021 | ||||||
Actual Primary Completion Date | October 3, 2022 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Radiographic Progression Free Survival (rPFS) [ Time Frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis) ] rPFS is defined as the time to radiographic progression by PCWG3-modified RECIST v1.1 (as assessed by Blinded independent central review) or death.
|
||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
|
||||||
Original Secondary Outcome Measures ICMJE |
|
||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | 177Lu-PSMA-617 vs. Androgen Receptor-directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer | ||||||
Official Title ICMJE | PSMAfore: A Phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Naïve Men With Progressive Metastatic Castrate Resistant Prostate Cancer | ||||||
Brief Summary | The purpose of this study is to determine whether 177Lu-PSMA-617 improves the rPFS or death compared to a change in ARDT in mCRPC participants that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or mHSPC settings. Approximately 450 participants will be randomized (225 per treatment group). |
||||||
Detailed Description | This is a phase III, open label, multicenter randomized study where it is considered appropriate to delay taxane-based chemotherapy. The study aims at evaluating the superiority of 177Lu-PSMA-617 over a change of ARDT treatment in prolonging rPFS. The primary endpoint of rPFS will be assessed via blinded independent centralized review of radiographic images provided by the treating physician and as outlined in PCWG3 Guidelines. The study will also evaluate whether 177Lu-PSMA-617 improves the overall survival (OS) in participants with progressive PSMA-positive mCRPC compared to participants treated with a change in ARDT treatment. OS is defined as the time from randomization to death due to any cause. Treatment duration: approximately 43 months. Screening period At screening, the participants will be assessed for eligibility and will undergo a 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized. Randomization period The participants will be randomized 1:1 to receive 177Lu-PSMA-617 or a change of the ARDT treatment. The ARDT change will include approved Androgen Receptor (AR) axis targeted therapy (abiraterone or enzalutamide). Supportive care will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT). Investigational agents, biological products, immunotherapy, cytotoxic chemotherapy, other systemic radioisotopes (e.g. radium-223), Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors or hemi-body radiotherapy treatment must not be administered during the study treatment period. ARDT must not be administered concomitantly with 177Lu-PSMA-617. Treatment period • 177Lu-PSMA-617 treatment arm Participants randomized to the investigational arm will receive 7.4 GBq +/- 10% of 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT, may be used. After the last day of study treatment period of 177Lu-PSMA-617 (i.e. after completion of 6 cycles of treatment OR treatment discontinuation for any reason), the participants must have an End of Treatment (EOT) visit and enter the Post-treatment Follow-up. • ARDT treatment arm For participants randomized to the ARDT treatment arm, the change of ARDT treatment for each participant will be selected by the treating physician prior to randomization and will be administered per the physician's orders. Best supportive care, including ADT, may be used. After the last day of study treatment (treatment discontinuation for any reason) or upon radiographic progression as assessed by blinded centralized review, the participants must have an End of Treatment (EOT) and enter the Post-treatment Follow-up. End of Treatment Randomized treatment may be discontinued if:
It is important that the scheduled imaging assessments continue until BICR-determined progression. PSA progression is strongly discouraged as a criterion for initiation of a new neoplastic therapy prior to BICR-determined progression. PCWG3 guidelines should be followed to guide discontinuation of treatment. End of Treatment visit must be performed ≤ 7 days after the last day of study treatment period. EOT is to occur before the participant is to enter the post-treatment Follow-up period of the study and before the initiation of any subsequent anticancer treatment, outside of what is allowed in the study. If a participant withdraws consent for the treatment period of the study, an EOT must be done and the participant will enter the Post-treatment Follow-up unless he specifically withdraws post-treatment Follow-up. Crossover period Upon confirmation of rPFS by BICR, participants randomized to the ARDT arm will either be allowed to crossover to receive 177Lu-PSMA-617 within 28 days of central confirmation of radiographic progression or may continue to receive any other therapy per the discretion of the treating physician in the Post-treatment Follow-up. In order for a participant randomized to the change in ARDT arm to cross over to receive 177Lu-PSMA-617, he must meet the following criteria:
A participant, who is deemed to have disease progression per investigator assessment, but not by BICR, is not eligible to crossover at that time. Such participant should continue to receive randomized study treatment until progression determined by BICR. If crossover to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as for participants who were initially randomized to receive 177Lu-PSMA-617. After the last day of study treatment period of 177Lu-PSMA-617 or upon second radiographic progression (rPFS2), the participants must have a second End of Treatment (EOT2) and enter the Post-treatment Follow-up. The participant can receive any other therapy per the discretion of the treating physician in the Post-treatment Follow-up. Post-treatment Follow-up period
In long term follow-up safety and efficacy information will be collected:
The long-term follow-up period will also include the collection of survival information and other assessments. Other: Other data collected during long-term follow-up includes short physical exam, blood sampling for hematology, chemistry testing, coagulation, DNA and tumor samples for biomarkers. The visits will be carried out every 12 weeks (± 28 days) until death, lost to follow-up, withdrawal of consent or accrual of the number of events required for the planned analyses for OS for the study, whichever occurs first. This follow-up will allow to collect information on medically significant long-term toxicities such as long-term radiotoxicity. Duration of long term follow-up is expected to continue till end of study. Participants who have received 177Lu-PSMA-617 and remain in follow-up on the trial at the sponsor's completion of the study will be asked to join a separate study of long-term safety for a duration of up to 10 years If the participant withdraws consent for the collection of blood samples, PROs, and imaging assessments during the long-term follow-up, information on survival and AEs per above will be collected. |
||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 3 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Patients randomized to ARDT treatment have an option to crossover to 177Lu-PSMA-617 treatment after rPFS. Masking: Single (Outcomes Assessor)Masking Description: No masking. Primary Purpose: Treatment
|
||||||
Condition ICMJE | Prostatic Neoplasms | ||||||
Intervention ICMJE |
|
||||||
Study Arms ICMJE |
|
||||||
Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||
Actual Enrollment ICMJE |
469 | ||||||
Original Estimated Enrollment ICMJE |
450 | ||||||
Estimated Study Completion Date ICMJE | September 30, 2025 | ||||||
Actual Primary Completion Date | October 3, 2022 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
7a. Participants must have progressed only once on prior second generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide).
Exclusion Criteria:
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 therapy, 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:
In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF. 14a. Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: Participant with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed. 15. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study. 16. Any condition that precludes raised arms position. 17a. Eligible for treatment(s) other than ARDT based on presence of any mutations or biomarkers that are known as predictors of better response (e.g., AR-V7 or BRCA). 18. Not able to understand and to comply with study instructions and requirements. |
||||||
Sex/Gender ICMJE |
|
||||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Austria, Belgium, Canada, Czechia, France, Germany, Netherlands, Poland, Slovakia, Spain, Sweden, Switzerland, United Kingdom, United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04689828 | ||||||
Other Study ID Numbers ICMJE | CAAA617B12302 2020-003969-19 ( EudraCT Number ) |
||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
|
||||||
IPD Sharing Statement ICMJE |
|
||||||
Current Responsible Party | Novartis ( Novartis Pharmaceuticals ) | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Novartis Pharmaceuticals | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
|
||||||
PRS Account | Novartis | ||||||
Verification Date | March 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |