Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Kennedy Disease

All Drugs and Chemicals

Gallium 68 PSMA-11

Androgens

Pluvicto

Radiopharmaceuticals

Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. ADT must be ongoing; Best supportive care is allowed.

Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. In addition of SOC (ADT plus choice of ARPI as per physician's decision), Best supportive care is allowed.

Administration intravenously once every 6 weeks (1 cycle) for 6 cycles

AAA617

Single intravenous dose of approx. 150 Megabecquerel (MBq) prior PSMA-PET scans

AAA517

Single intravenous dose of approx. 333 Megabecquerel (MBq) prior PSMA-PET scans

Piflufolastat F 18

Enzalutamide, Darolutamide, Apalutamide as prescribed by the local investigator

ARPI

Best supportive care

Novartis Pharmaceuticals

McKayla Kortus

Luke Nordquist

The purpose of this study is to evaluate the efficacy and safety of AAA617 alone (Lutetium \[177Lu\] vipivotide tetraxetan) and in combination with an Androgen Receptor Pathway Inhibitors (ARPI) in participants with PSMA-positive, castration-resistant prostate cancer and no evidence of metastasis in conventional imaging (CI) (i.e., CT/MRI and bone scans). Approximately 120 participants will be randomized.

A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC

An International Prospective Open-label, Multi-center, Randomized, Non-comparative Phase II Study of Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) Alone and Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) in Combination With Androgen Receptor Pathway Inhibitors in Patients With PSMA PET Scan Positive Castration-Resistant Prostate Cancer

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

PSA response is defined as the time of PSA nadir value of =\< 0.2 ng/mL is confirmed by a second (the next) PSA measurement at least 4 weeks later

MFS is defined as the time from date of randomization to the first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging using RECIST 1.1 or death.

rPFS is defined as the time from the date of randomization to the date of first documented radiographic disease progression by conventional imaging assessed using RECIST 1.1 or death.

OS defined as date of death due to any cause

PFS2 defined as time from the date of randomization to the date of first documented disease progression by investigator's assessment (PSA, radiographic, symptomatic, or any combination) on next line of therapy subsequent to MFS event or death due to any cause, whichever occurs first

Time to symptomatic progression will be defined as the time from the date of randomization to the date of first documented event for any of the following:

* Development of a symptomatic skeletal event (SSE)
* Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy
* Development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy

Time to initiation of cytotoxic chemotherapy will be defined as the time from the date of randomization to the date of first documented dose of new cytotoxic chemotherapy being administered to the participant

TTSSE is defined as the time from the date of randomization to the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death due to any cause, whichever occurs first

Time to distant metastasis development is defined as the time from the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging using RECIST 1.1

Time to local radiological progression is defined as the time from the date of randomization to the date of first documented local radiographic disease progression by conventional imaging using RECIST 1.1

Time to initiation or change in therapy is defined as the time from the date of randomization to the date of first documented dose of a new / change in therapy being administered to the participant

Time to PSA response is calculated as the time from randomization to PSA response with a PSA nadir value of =\< 0.2ng/mL.

PSA50 response is defined as the proportion of participants who have a \>= 50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement \>= 4 weeks later

PSA90 response is defined as the proportion of participants who have a \>= 90% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement \>= 4 weeks later

FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACTGeneral (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

The FACT-RNT is assessing treatment-related symptoms of special interest/associated with Radionuclides Therapies. The FACT-RNT contains 15 items assessing dry mouth, dry eyes, difficulty urinating, nausea, vomiting, diarrhea, constipation, loss of appetite, fatigue, impact of fatigue, pain, bone pain, pain interference, bothered by of side effects of treatment and isolation due to illness or treatment.

The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item selfreport questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 \[no pain\] to 10 \[pain as bad as you can imagine\]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.

Antineoplastic Agents

Taxane

Patients will receive the investigational product 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) may be used

Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles.

[177Lu]Lu-PSMA-617

Best supportive/best standard of care as defined by the local investigator

Best supportive/best standard of care (BS/BSOC)

single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 259 MBq (3 - 7 mCi).

68Ga-PSMA-11

The purpose of this study is to assess the efficacy, safety, tolerability, Pharmacokinetic(s) (PK) and dosimetry of \[177Lu\]Lu-PSMA-617 when administered in addition to Best Supportive/Best Standard of Care (BSC/BSoC) in Chinese participants with progressive PSMA-positive mCRPC who received at least 1 novel androgen receptor pathway inhibitor (ARPI) and were previously treated with 1 to 2 taxane regimens. Furthermore, the safety, PK, and dosimetry of \[68Ga\]Ga-PSMA-11 are assessed.

Data from this study will be used to bridge global pivotal phase III study (VISION, AAA617A12301) and to support China registration of \[177Lu\]Lu-PSMA-617 as a novel anticancer modality, namely radioligand therapy, in mCRPC.

This is a 2-part study:

1. Main part: Approximately 30 participants with at least 1 measurable lesion by PCWG3-modified RECIST v1.1 criteria will be enrolled in the main part. The primary endpoint of confirmed ORR will be analyzed with participants in this part, and will be assessed via independent centralized review of radiographic images provided by the Investigator and as outlined in PCWG3-modified RECIST v1.1 criteria.
2. Extension part: The extension part will enroll additional 30 participants with or without measurable lesions following the main part. The secondary endpoints will be analyzed with all participants in both main part and extension part.

Screening and enrollment period:

Written informed consent form (ICF) must be obtained prior to any screening procedures. All screening procedures described in the Assessment Schedule must be completed within 28 days prior to enrollment, except for radiographic imaging assessment, which must be done within 21 days prior to enrollment.

The participants will be assessed for eligibility and will undergo a mandatory \[68Ga\]Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan to evaluate Prostate-specific Membrane Antigen (PSMA) positivity for eligibility as assessed by central readers. Only participants with PSMA positive cancer and confirmed eligibility criteria will be enrolled.

Following completion of all required screening procedures and verifying participant eligibility, the participant will be enrolled. \[177Lu\]Lu-PSMA-617 will be ordered in parallel with interactive response technology (IRT) enrollment registration to allow at least 2 weeks to order and deliver \[177Lu\]Lu-PSMA-617.

Treatment period:

In principle, all participants should begin \[177Lu\]Lu-PSMA-617 dosing within 14 days after enrollment registration. However, Cycle 1 Day 1 (C1D1) can be delayed by up to an additional 3 days only for unexpected scheduling delays. Participants will receive 7.4 Gigabecquerel (GBq) (200 Millicuries (mCi)) +/- 10% \[177Lu\]Lu-PSMA-617 once every 6 weeks for a planned 6 cycles. BSC/BSoC may be used, including available care for the eligible participants according to best institutional practice. ARPIs (e.,g., abiraterone, etc.) are allowed. BSC/BSoC for each participant will be selected at the discretion of the Investigator prior to \[177Lu\]Lu-PSMA-617 administration, and can be modified over time as needed. BSC/BSoC will be administered per the physician's orders according to clinical best practice.

Radiographic imaging (CT with contrast/Magnetic Resonance Imaging (MRI) and bone scan) will be done at every 8 weeks (± 4 days) after first dose of \[177Lu\]Lu-PSMA-617 for the first 24 weeks (independent of dose delays), then every 12 weeks (± 4 days) thereafter and at End of Treatment (EOT) Visit (if not done within 28 days of EOT) until radiographic disease progression confirmed by central reader, death, withdrawal of consent, loss to follow-up, or subject/guardian's decision.

After the last day of study treatment period of \[177Lu\]Lu-PSMA-617 (i.e. after completion of 6 cycles of treatment OR treatment discontinuation for any reason) \[e.g. upon radiographic progression as confirmed by blinded independent centralized review\]), the participants must have an EOT visit performed ≤ 7 days and enter into the Post-treatment Follow-up period.

If a participant withdraws consent for the treatment period of the study, an EOT must be done and the participant will enter into the Post-treatment Follow-up unless he specifically withdraws consent for post-treatment Follow-up.

Post-treatment Follow-up period:

1. 30-day Safety Follow-up. All treated participants should have a safety follow-up conducted approximately 30 days after EOT visit.
2. Long term Follow-up. The long-term follow-up starts after the 30-day Safety follow-up and lasts until study completion. If a participant in the long term follow-up period discontinues treatment for reasons other than BICR-determined radiographic progression, his tumor assessments must be performed every 8 weeks after first dose of study treatment for the first 24 weeks (week 9, 17, 25) and then every 12 weeks (week 37, 49, etc) until confirmation of radiographic progression by BICR. The long-term follow-up period will also include the collection of survival and treatment updates, patient reported outcomes (PROs), serious adverse events (suspected to be related to study treatment), as well as blood sampling for hematology, chemistry testing, coagulation, and PSA. The visits will be carried out every 12 weeks (± 4 weeks) until death, lost to follow-up, withdrawal of consent, opposition to use data/biological samples or study completion, whichever occurs first. This follow-up will allow the data collection on medically significant long-term toxicities, such as long-term radiotoxicity.

If the participant withdraws consent for the collection of blood samples, PROs, and imaging assessments during the long-term follow-up, the information on survival, serious adverse events (SAEs) related to study treatment and post-treatment antineoplastic therapy will be collected.

PK/dosimetry assessments:

Both PK and dosimetry of \[68Ga\]Ga-PSMA-11 will be evaluated in at least 10 and up to 12 participants (at least 6 participants in main part). PK and dosimetry of \[68Ga\]Ga-PSMA-11 can be evaluated in any participant regardless of his PSMA status.

Both PK and dosimetry of \[177Lu\]Lu-PSMA-617 will be evaluated in at least 10 and up to 12 participants (at least 6 participants in main part).

Participants who take part in PK and dosimetry evaluation of \[177Lu\]Lu-PSMA-617 will also take part in the efficacy and safety evaluation together with the other participants. The treatment and assessment procedure follow the same as above.

A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive mCRPC

A Prospective, Open-label, Multi-center, Single-arm, Phase II Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com

Confirmed Overall Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR is based on PCWG3-modified RECIST v1.1 response for patients with measurable disease at baseline.

Radiographic progression free survival (rPFS) is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death

Overall survival (OS) is defined as the time from the date of enrollment to the date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date).

Overall response rate (ORR)is defined as the proportion of participants with best overall response of complete response or partial response in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

Disease control rate (DCR) is defined as the proportion of participants with best overall response of complete response or partial response or Stable disease in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

Duration of response (DOR) is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause.

Time to a first symptomatic skeletal event (TTSSE) is 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.

PSA response rate is the proportion of PSA responders, defined as a participant who has achieved PSA decrease of \>= 50% from baseline that is confirmed by a second consecutive PSA measurement \>= 4 weeks later. Determination of response status will be based on PCWG3 recommendations.

Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first.

EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.

The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[177Lu\]Lu-PSMA-617 in at least 10 and up to 14 patients. AUClast will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[177Lu\]Lu-PSMA-617 in at least 10 and up to 14 patients. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[177Lu\]Lu-PSMA-617 in at least 10 and up to 14 patients. Blood concentration of \[177Lu\]Lu-PSMA-617 will be summarized with descriptive statistics.

The quantity of ionizing radiation absorbed by organs and tissues will be summarized with descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[68Ga\]Ga-PSMA-11 in at least 10 and up to 14 patients. AUClast will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[68Ga\]Ga-PSMA-11 in at least 10 and up to 14 patients. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[68Ga\]Ga-PSMA-11 in at least 10 and up to 14 patients. Blood concentration of \[68Ga\]Ga-PSMA-11 will be summarized with descriptive statistics.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC	NCT05849298	Prostatic Neopl...	AAA617 AAA517 Piflufolastat F... ARPI ADT Best supportive...	18 Years -	Novartis
A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC	NCT05849298	Prostatic Neopl...	AAA617 AAA517 Piflufolastat F... ARPI ADT Best supportive...	18 Years -	Novartis
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive mCRPC	NCT05670106	Metastatic Cast...	[177Lu]Lu-PSMA-... Best supportive... 68Ga-PSMA-11	18 Years -	Novartis
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive mCRPC	NCT05670106	Metastatic Cast...	[177Lu]Lu-PSMA-... Best supportive... 68Ga-PSMA-11	18 Years -	Novartis

Spots Global Cancer Trial Database for arpi

Every month we try and update this database with for arpi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for arpi

Every month we try and update this database with for arpi cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for arpi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.