Save

An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.

PHASE3RECRUITING

The purpose of this study is to evaluate the efficacy and safety of lutetium (177Lu) vipivotide tetraxetan (AAA617) in participants with oligometastatic prostate cancer (OMPC) progressing after definitive therapy to their primary tumor. The data generated from this study will provide evidence for the treatment of AAA617 in early-stage prostate cancer patients to control recurrent tumor from progressing to fatal metastatic disease while preserving quality of life by delaying treatment with androgen deprivation therapy (ADT).

Simpliy with AI

Study details:

All participants will be assessed for eligibility and will undergo baseline disease assessments including a mandatory gallium (68Ga) gozetotide (also known as \[68Ga\]Ga-PSMA-11) or piflufolastat (18F) ( also known as\[18F\]DCFPyL) PET/CT scan and conventional imaging (i. e. , CT/MRI and bone scans).

Piflufolastat (18F) PET/CT scan will be performed in countries where it is approved. Stereotactic Body Radiation Therapy (SBRT) will be administered to all metastatic Prostate Cancer (PC) lesions after randomization and before the start of treatment with AAA617 or observation. * The duration of SBRT procedures is approximately 3 weeks.

* For participants randomized to the investigational arm (AAA617), the treatment duration will be up to 4 cycles of AAA617. For participants randomized to the control arm (observation) the treatment duration will end at the last fraction of SBRT administration. * The visit frequency will be every week 1 and 3 of each of the 4 cycles and every 16 weeks thereafter (for both arms) until first event of disease progression (RECIST 1.

1). * The study duration is approximately 6. 5 years.

Simplify with AI

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Histologically confirmed prostate cancer prior to randomization

Participants must have biochemically recurrent disease after definitive treatment to prostate by Radical Prostatectomy ((RP), (alone or with post-operative radiation to prostate bed/pelvic nodes)) or External beam Radiation Therapy (XRT), (prostate alone or prostate with seminal vesicle and/or pelvic nodes) and/or brachytherapy prior to randomization. Biochemical recurrence is defined as: nadir PSA + 2 ng/mL post XRT (if participant received-radiation therapy to intact prostate) and PSA > 0.2 ng/mL and rising post RP (with or without post-operation Radiation Therapy (RT))

Participants must have OMPC with =\< 5 PSMA-positive metastatic lesions on screening PSMA PET/CT scan (with either gallium (68Ga) gozetotide or piflufolastat (18F)) as visually assessed by BIRC based on the methodology proposed in the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE v2) (Seifert et al 2023); for further details, please refer to Section 8.1 and the Imaging Manual. Metastatic lesions may include regional/pelvic lymph nodes (N1), distant lymph nodes (M1a), bone (M1b), lung and others visceral (M1c) except liver and brain classified using AJCC 8. When counting the number of oligometastatic lesions, each lesion is counted as distinct metastasis irrespective of its anatomical location (e.g., one pelvic and one extra-pelvic lymph node will be counted as two metastatic lesions)

At least 1 PSMA-positive lesion should be a distant metastasis (M1) per AJCC8 classification at screening. For AJCC M staging, PSMA PET information should be used

Participants must have a negative conventional imaging for M1 disease at screening.

All metastatic lesions detected at screening should be amenable to SBRT

Non-castration testosterone level >100 ng/dL at screening

Exclusion criteria

Participants with de novo OMPC at screening

Unmanageable concurrent bladder outflow obstruction or urinary incontinence at screening. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed

Prior therapy with: ADT including bilateral orchiectomy. Participants who had XRT or RP and completed adjuvant ADT (or ADT+ARPI) prior to recurrence are eligible to participate if the last dose of ADT (or ADT+ARPI) was before 12 months from randomization. Participants who had prior SBRT with short term ADT (3-6 months) are also allowed if the ADT was stopped at least 12 months before randomization. Participants who discontinued ADT due to disease progression are not allowed (i.e., Castration-Resistant Prostate Cancer (CRPC) participants); Other hormonal therapy. e.g. Use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethimide) if used in the context of prostate cancer treatment. Same medications are allowed if used for other indications: e.g., Benign Prostatic Hyperplasia (BPH), if stopped at least 5 half-lives before randomization; First-generation anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone); Second generation anti-androgens (e.g., enzalutamide, apalutamide and darolutamide); CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galeterone, ketoconazole). Short term ketoconazole treatment (<28 days) is permitted; Radiopharmaceutical agents (e.g., Strontium-89, PSMA-targeted radioligand therapy); Immunotherapy (e.g., sipuleucel-T); Chemotherapy, except if administered in the adjuvant/neoadjuvant setting completed > 12 months before randomization; Any other investigational or systemic agents for metastatic disease

Radiation therapy external beam radiation therapy (EBRT) and brachytherapy within 28 days before randomization

Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, hormonal therapy (see ADT initiation guidance in Section 6.8.2), Poly Adenosine Diphosphate-Ribose Polymerase (PARP) inhibitor, biological therapy or investigational therapy

Diagnosed at screening with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease/treatment free for more than 3 years are eligible, as are participants with adequately treated non-melanoma skin cancer and superficial bladder cancer.

History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree Atrioventricular (AV) block without a pacemaker; History of familial long QT syndrome or known family history of Torsades de Pointe

Participants in immediate need of ADT as assessed by the investigator.

Simplify with AI

Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: Male

Things to know

Study dates

Study start: 2024-03-12

Primary completion: 2027-12-21

Study completion finish: 2030-07-09

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT05939414

Intervention or treatment

DRUG: AAA617

Conditions

• Oligometastatic Prostate Cancer (OMPC)

Image related to Oligometastatic Prostate Cancer (OMPC)

Condition: Oligometastatic Prostate Cancer (OMPC)
DRUG: AAA617
Adelaide, South Australia, Australia
Sponsor: Novartis Pharmaceuticals

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Novartis Investigative Site

Research sites nearby

Select from list below to view details:

Novartis Investigative Site
Adelaide, South Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Investigational Arm: lutetium (177Lu) vipivotide tetraxetan (AAA617) All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by a dose of 7.4 GBq (200 mCi) +/- 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for a planned 4 cycles.	DRUG: AAA617 Stereotactic Body Radiation Therapy (SBRT) followed by AAA617 will be administered once every 6 weeks (1 cycle) for a planned 4 cycles to participants randomized to the Investigational arm
NO_INTERVENTION: Control arm: observation (watchful waiting) All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by observation only.	Not specified

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS)	Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS) is defined as the time from randomization to first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) and bone scans) as assessed by BIRC using RECIST 1.1 or death due to any cause, whichever occurs first. Participants who are alive without distant metastasis at the analysis data cut-off or are lost to follow-up at the time of analysis will be censored for MFS at the time of their last adequate radiographic assessment. Clinical deterioration without objective radiographic evidence will not be considered as documented distant metastasis.	From date of randomization until first evidence of radiographically detectable bone or soft tissue distant metastasis or death due to any cause, whichever occurs first, assessed up to approximately 30 months

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Key secondary endpoint: Time to Hormonal Therapy (TTHT)	Time to Hormonal Therapy (TTHT) is defined as the time from randomization to the time to Androgen Deprivation Therapy (ADT). The type of hormonal therapy will be at the discretion of the Investigator.	From date of randomization until date of Androgen Deprivation Therapy (ADT), assessed up to approximately 74 months
Investigator assessed Metastasis Free Survival (MFS)	Investigator assessed Metastasis Free Survival (MFS) is defined as the time from randomization to the first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., CT/MRI and bone scans) as assessed by Investigator using RECIST 1.1 or death from any cause, whichever occurs first.	From date of randomization until first evidence of radiographically detectable bone or soft tissue distant metastasis or death from any cause, whichever occurs first, assessed up to approximately 74 months
Time to prostate specific antigen (PSA) progression (TTPSAP)	Time to prostate specific antigen (PSA) progression (TTPSAP) is defined as time from randomization to first PSA progression 1. First PSA progression 1 is defined as a rising PSA confirmed on repeated measurement at least 3 weeks later, and at least greater than 25% and \>= 2 ng/mL above nadir or baseline, whichever is lower. In the absence of PSA progression, TTPSAP will be censored at the last PSA measurement.	From date of randomization until date of first PSA progression, assessed up to approximately 74 months
Radiographic Progression Free Survival (rPFS)	Radiographic progression free survival (rPFS) is defined as the time from randomization to first documentation of confirmed radiographic progressive disease or death due to any cause (whichever occurs first) by conventional imaging (i.e., CT/MRI and bone scans) using RECIST 1.1. The rPFS will be analyzed based on BIRC and Investigator assessments respectively.	From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 74 months
Time to next therapy (local or systemic)	Time to next therapy (local or systemic) is defined as the time from randomization to initiation of the next line of therapy (local or systemic). Next-line therapy is defined as the first new (local or systemic) anti-neoplastic therapy initiated after discontinuation of study treatment regardless of end of treatment (EOT) reason.	From date of randomization until initiation of the next line of therapy (local or systemic), assessed up to approximately 74 months
24-month prostate-specific antigen (PSA) progression free survival (PFS)	24-month PSA PFS is defined as PSA PFS at 24 months. PSA PFS is defined as the time from date of randomization to the date of first documented PSA progression 2 or death from any cause, whichever occurs first. PSA progression 2 is defined as a PSA concentration above the nadir (or baseline if lower) of \>= 0.5 ng/mL, confirmed by repeated measurement at least 3 weeks later. PSA PFS will be censored if no PSA PFS event is observed before the first to occur analysis cut-off date. The censoring date will be the date of the last adequate tumor assessment prior to cut-off.	From date of randomization until date of first documented PSA progression 2 or death from any cause, whichever occurs first, assessed up to approximately 74 months
Time to symptomatic progression	Time to symptomatic progression is defined as time from randomization to the date of first documented event for any of the following, whichever occurs first: development of symptomatic skeletal event, escalation in cancer-related pain or worsening of disease-related symptoms leading to the initiation of a new systemic anticancer therapy, development of clinically significant symptoms due to local or regional tumor progression leading to surgery or radiation therapy.	From date of randomization until date of first documented symptomatic progression, assessed up to approximately 74 months
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire	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.	From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT) Questionnaire	The FACT-RNT (Functional Assessment of Cancer Therapy - Radionuclide Therapy) is a Patient Reported Outcomes (PRO) new measure developed using FACIT specific questions (items), selected from FACIT item bank, to assess treatment-related symptoms of special interest associated with radioligand therapies. The FACT-RNT contains items assessing dry mouth, dry eyes, vomiting, diarrhea, constipation, loss of appetite, fatigue, impact of fatigue, bone pain, and isolation due to illness or treatment. FACT-RNT score range 0 to 60, with higher score indicating better quality of life.	From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Brief Pain Inventory - Short Form (BPI-SF) Questionnaire	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.	From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L)	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.	From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Time to First Symptomatic Skeletal Event (TTSE)	Time to first symptomatic skeletal event (TTSSE) is defined as date of randomization to the date of first new SSE or death from any cause, whichever occurs first. Symptomatic skeletal events (SSE) will be defined by the occurrence of any of the following (whichever occurs earlier): symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain.	From date of randomization till end of treatment (EOT) or death, whichever happens first, assessed up to approximately 74 months
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.	From date of randomization up till 42 day safety Follow-up, assessed up to approximately 74 months
Dose modifications and intensity for AAA617	Dose modifications (dose interruptions and reductions) and dose intensity for AAA617 will be assessed and summarized using descriptive statistics.	From date of randomization until end of treatment (EOT), assessed up to approximately 30 months
Overall survival (OS)	Overall Survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. OS time for participants who are alive at the end of the study or are lost to follow-up will be censored at the date of last contact.	From date of randomization until date of death from any cause, assessed up to approximately 74 months

Frequently Asked Questions

Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

No questions submitted. Be the first to ask a question!

You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

Clinical Trials Gov: An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.