NCT Number: NCT06855277
The purpose of this study is to determine whether [225Ac]Ac-PSMA-617 (AAA817), given for up to 6 cycles at a dose of 10 Megabecquerel (MBq) +/- 10%, plus androgen receptor pathway inhibitor (ARPI), improves the radiographic progression free survival (rPFS) compared to investigator's choice of standard of care (SOC) (ARPI change or taxane-based chemotherapy or [177Lu]Lu-PSMA-617 (AAA617)) in adult participants with PSMA-positive metastatic castration resistant prostate cancer (mCRPC) treated with another ARPI as last treatment and who have not been exposed to a taxane-containing chemotherapy in the mCRPC setting nor have received any prior PSMA-targeting radioligand therapy.
Interested in participating?
Request Info18 year–100 year
Male
Interventional
Phase 3
Novartis Investigative Site, Darlinghurst, New South Wales, Australia
This is a phase III, open label, multicenter randomized study. The study aims at evaluating the superiority of 225Ac-PSMA-617 combined with androgen receptor pathway inhibitor (ARPI) over a change of ARPI or chemotherapy or [177Lu]Lu-PSMA-617 (AAA617) in prolonging progression free survival (rPFS).
Screening period: At screening, the participants will be assessed for eligibility and will undergo a 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.
Participants randomized to the investigational arms will receive up to 6 doses of AAA817 10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral abiraterone) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria.
Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or [177Lu]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion following local guidelines as per standard of care and product labels and adhere to the protocol end of treatment criteria.
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).
Safety will be assessed routinely during the study. Crossover is not allowed among study arms.
The study will be conducted in the USA among other countries globally.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.
Other protocol-defined inclusion/exclusion criteria may apply.
AAA817 is being studied for treating PSMA positive mCRPC. Inside the body, it attaches itself to PSMA on the cell surface of the prostate cancer cells and emits radiation to kill them. This treatment is also called a radioligand therapy.
Other names: [225Ac]Ac-PSMA-617
Androgen receptor pathway inhibitor (ARPI): An ARPI is approved for the treatment of prostate cancer. It works by blocking signals from male hormones, such as testosterone, that helps cancer cells grow. By blocking these signals, an ARPI slows down or stops the growth of prostate cancer cells. In this trial, participants will be given either enzalutamide or abiraterone.
Other names: Enzalutamide or Abiraterone
Standard treatment includes approved treatment for mCRPC. In this trial, the trial doctor will decide which available treatment participants will receive. The trial doctor will select either an ARPI of enzalutamide or abiraterone, or a taxane based chemotherapy of docetaxel or cabazitaxel or [177Lu]Lu-PSMA-617 (AAA617).
Other names: ARPI enzalutamide, ARPI abiraterone, Taxane based chemotherapy of docetaxel, Taxane based chemotherapy of cabazitaxel, [177Lu]Lu-PSMA-617 (AAA617)
Time frame: From the date of randomization to the date of the first documented radiographic disease progression using conventional imaging, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Time to radiographic disease progression or death due to any cause.
Time frame: From the date of randomization to the date of death due to any cause, assessed up to approximately 40 months.
Time to death due to any cause.
Time frame: From date of randomization to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Time to radiographic disease progression, using by blinded independent central review (BICR) using conventional imaging and Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 criteria or death due to any cause.
Time frame: From the date of randomization to the date of death due to any cause.
Time to death due to any cause.
Time frame: From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
rPFS time to the date of first documented radiographic disease progression or death due to any cause, whichever occurs first.
Time frame: From date of randomization to the first documented progression by investigator's assessment or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Time to first documented progression or death due to any cause.
Time frame: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to approximately 40.0 months.
Time to first documented progression on next line of antineoplastic therapy or death from any cause.
Time frame: From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
The proportion of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in soft tissue.
Time frame: From the date of randomization to the date of the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
The proportion of participants with BOR of confirmed CR, PR, stable disease (SD) or non-CR/non-progressive disease (PD) in soft tissue.
Time frame: From the date of first documented response (CR or PR) for confirmed responders and the date of first documented radiographic progression in soft tissue or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Time between the date of first documented response and the date of first documented radiographic progression or death due to any cause.
Time frame: From the date of randomization to the date of radiographic soft tissue progression or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Time to radiographic soft tissue progression.
Time frame: From the date of randomization to the date of the first documented radiographic disease progression, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Time to date of first new symptomatic skeletal event of death due to any cause.
Time frame: From the date of randomization to the date of safety follow up, assessed up to approximately 40.0 months.
The percentage of participants who achieved ≥ 50% and ≥ 90% decrease from baseline, respectively.
Time frame: From Cycle 1 Day 1 up to approximately cycle 5 days 11 (each cycle is 8 weeks).
Time-concentration profiles and PK parameters of AAA817 (e.g. AUC, Cmax).
Time frame: From randomization to the first occurrence of worsening on the score or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Change from baseline on FACT-P Prostate Cancer Subscale (PCS). FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment.
Time frame: From randomization to the first occurrence of worsening from baseline, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.
Time to worsening on the Worst Pain is defined as the time from randomization to the first occurrence of worsening on the Worst Pain item (BPI-SF) or death due to any cause, whichever occurs first.
Contact information is provided by the study sponsor or research team.
Novartis Pharmaceuticals
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Novartis Pharmaceuticals
CONTACT
Novartis Pharmaceuticals
Industry
A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer
Acronym: AcTFirst
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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