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

Phase 2
Recruiting
Conditions
Prostatic Neoplasm
Interventions
Registration Number
NCT05849298
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
120
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm AAAA617Participants 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.
Arm AAAA517Participants 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.
Arm AADTParticipants 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.
Arm BPiflufolastat F 18Participants 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.
Arm APiflufolastat F 18Participants 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.
Arm ABest supportive careParticipants 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.
Arm BAAA617Participants 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.
Arm BARPIParticipants 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.
Arm BAAA517Participants 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.
Arm BBest supportive careParticipants 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.
Arm BADTParticipants 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.
Primary Outcome Measures
NameTimeMethod
PSA responseFrom randomization until PSA nadir value of =< 0.2 ng/mL that is confirmed by a second (the next) PSA measurement >= 4 weeks later, up to 5 years

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

Secondary Outcome Measures
NameTimeMethod
Time to initiation of cytotoxic chemotherapyFrom the date of randomization to the date of first documented dose of new cytotoxic chemotherapy administered to the participant, up to 5 years

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

Time to distant metastasis developmentFrom the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis, up to 5 years

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 progressionFrom the date of randomization to the date of first documented local radiographic disease progression, up to 5 years

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 therapyFrom the date of randomization to the date of first dose of a new / change in therapy, up to 5 years

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 responseFrom randomization to PSA response, up to 5 years

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

Radiographic Progression Free Survival (rPFS)From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, up to 5 years

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.

Metastatic Free Survival (MFS)From date of randomization until date of progression or date of death whichever occurs first, up to 5 years

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.

Overall Survival (OS)From date of randomization until date of death from any cause, up to 5 years

OS defined as date of death due to any cause

Time to first symptomatic skeletal event (TTSSE)From the date of randomization to the date of the first new symptomatic pathological bone fracture, spinal cord compression, orthopedic surgical intervention, radiation therapy or death due to any cause, whichever occurs first, up to 5 years

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

PSA90 responseFrom date of randomization until end of efficacy follow-up, up to 5 years

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

second Progression Free Survival (PFS2)From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 5 years

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 progressionFrom date of randomization until development of a symptomatic skeletal event, new systemic anti-cancer therapy, surgical intervention or radiation therapy, whichever occurs first, up to 5 years

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

PSA50 responseFrom date of randomization until end of efficacy follow-up, up to 5 years

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

Functional Assessment of Cancer Therapy - Prostate (FACT-P)From date of randomization until end of efficacy follow-up, up to 5 years

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.

Functional Assessment of Cancer Therapy - Radiotherapies (FACT-RNT) QuestionnaireFrom date of randomization until end of efficacy follow-up, up to 5 years

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.

Brief Pain Inventory - Short Form (BPI-SF) QuestionnaireFrom date of randomization until end of efficacy follow-up, up to 5 years

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.

Trial Locations

Locations (15)

Urology Associates of Mobile

🇺🇸

Mobile, Alabama, United States

Rocky Mountain Cancer Centers

🇺🇸

Longmont, Colorado, United States

University Cancer and Blood Center LLC

🇺🇸

Athens, Georgia, United States

Unity Point Clinic

🇺🇸

Des Moines, Iowa, United States

Urology Cancer Center PC

🇺🇸

Omaha, Nebraska, United States

Associated Med Professionals of NY

🇺🇸

Syracuse, New York, United States

Oregon Urology Institute

🇺🇸

Springfield, Oregon, United States

Wellspan York Hospital

🇺🇸

York, Pennsylvania, United States

Carolina Urologic Research Center, LLC

🇺🇸

Myrtle Beach, South Carolina, United States

Urology Clinic of North Texas

🇺🇸

Dallas, Texas, United States

Univ of Texas Southwest Med Center

🇺🇸

Dallas, Texas, United States

Rio Grande Urology

🇺🇸

El Paso, Texas, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

UT Health San Antonio Mays Cancer Center

🇺🇸

San Antonio, Texas, United States

Novartis Investigative Site

🇪🇸

Madrid, Spain

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