Trial Title:
An Open-label Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan Versus Observation in PSMA Positive OMPC.
NCT ID:
NCT05939414
Condition:
Oligometastatic Prostate Cancer (OMPC)
Conditions: Official terms:
Prostatic Neoplasms
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Conditions: Keywords:
Lutetium (177Lu) vipivotide tetraxetan
Oligometastatic Prostate Cancer (OMPC)
Metastasis Free Survival (MFS)
gallium (68Ga) gozetotide
piflufolastat (18F)
prostate-specific membrane antigen (PSMA)
Delay Castration
Stereotactic Body Radiation Therapy (SBRT)
metastasis-directed therapy
Androgen Deprivation Therapy (ADT)-free survival.
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AAA617
Description:
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
Arm group label:
Investigational Arm: lutetium (177Lu) vipivotide tetraxetan (AAA617)
Other name:
(177Lu) vipivotide tetraxetan
Summary:
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).
Detailed description:
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.
Criteria for eligibility:
Criteria:
Key Inclusion criteria:
1. Histologically confirmed prostate cancer prior to randomization
2. 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))
3. 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)
4. 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
5. Participants must have a negative conventional imaging for M1 disease at screening.
Note:
- For a participant not to be eligible, CI positive M1 lesions should be
unequivocal in CI scans, i.e., potentially not attributable to findings thought
to represent something other than tumor (e.g., degenerative, or post-traumatic
changes or Paget's disease in bone lesions). For conventional imaging
assessments, bone lesions must be assessed by bone scan only and soft tissue
lesions must be assessed by CT/MRI scans only at screening.
- Prior knowledge of PSMA PET positivity should not influence the radiologist
(reader) in determination of CI positivity. Two different readers will be
involved, one reader for PSMA PET scan and one reader for CI: Reader will be
blinded to PSMA PET scan results while reading CI scans. Reader should not
modify their assessment of CI scans (e.g. changing a lesion previously
identified as equivocal in CI to unequivocal) after reading the PSMA PET scan.
Similarly, biopsy positivity should not influence the reader in the assessment
of CI positivity. More details on the reading paradigm will be provided in the
imaging charter
- MRI for radiation treatment planning may show M1 disease but this will not
exclude the participant from the study if the lesion is deemed negative per
baseline CT or bone scans
- Participants with pelvic disease (N1) seen in conventional imaging are allowed
if the local spread is below common iliac bifurcation (per AJCC 8 definition of
local disease)
- Distant lymph node disease (M1a) that is visible per CI and less than 10mm in
the short axis is not exclusionary irrespective of PSMA PET positivity.
- If a previously surgically removed lesion was unequivocal for M1 by bone scan
or CT, the participant is not eligible.
6. All metastatic lesions detected at screening should be amenable to SBRT
7. Non-castration testosterone level >100 ng/dL at screening
Key Exclusion criteria:
1. Participants with de novo OMPC at screening
2. 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
3. Prior therapy with:
1. 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)
2. 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
3. Radiopharmaceutical agents (e.g., Strontium-89, PSMA-targeted radioligand
therapy)
4. Immunotherapy (e.g., sipuleucel-T)
5. Chemotherapy, except if administered in the adjuvant/neoadjuvant setting
completed > 12 months before randomization
6. Any other investigational or systemic agents for metastatic disease
4. Radiation therapy external beam radiation therapy (EBRT) and brachytherapy within 28
days before randomization
5. 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
6. 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.
7. 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
8. Participants in immediate need of ADT as assessed by the investigator.
Other protocol defined Inclusion/Exclusion may apply.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Highlands Oncology Group .
Address:
City:
Fayetteville
Zip:
72703
Country:
United States
Status:
Recruiting
Contact:
Last name:
Stephanie Deboard
Phone:
+1 479 878 7098
Email:
sdeboard@hogonc.com
Investigator:
Last name:
Joseph Thaddeus Beck
Email:
Principal Investigator
Facility:
Name:
Rocky Mountain Cancer Centers Research
Address:
City:
Longmont
Zip:
80501
Country:
United States
Status:
Recruiting
Contact:
Last name:
Chrisit Davis
Phone:
303-338-4876
Email:
Christi.Davis@usoncology.com
Investigator:
Last name:
Allen Cohn
Email:
Principal Investigator
Facility:
Name:
Cancer Specialists of North Florida Research
Address:
City:
Jacksonville
Zip:
32256
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ryan Veldhuizen
Email:
Ryan.Veldhuizen@CSNF.us
Investigator:
Last name:
Richard Cassidy
Email:
Principal Investigator
Facility:
Name:
Johns Hopkins Kimmel Com Cancer Ctr Research
Address:
City:
Baltimore
Zip:
21231
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Ana Kiess
Email:
Principal Investigator
Facility:
Name:
BAMF Health
Address:
City:
Grand Rapids
Zip:
49503
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clayton McNamura
Email:
clayton.mcnamara@bamfhealth.com
Investigator:
Last name:
Brandon Mancini
Email:
Principal Investigator
Facility:
Name:
Profound Research LLC
Address:
City:
Royal Oak
Zip:
48073
Country:
United States
Status:
Recruiting
Contact:
Last name:
Catherine Maples
Email:
catherine.maples@profoundresearch.io
Investigator:
Last name:
Adam Gadzinski
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mathew Timm
Phone:
507-538-2155
Email:
Timm.mathew@mayo.edu
Investigator:
Last name:
Ryan Phillips
Email:
Principal Investigator
Facility:
Name:
Wash U School of Medicine .
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Konstantina Stavroulaki
Email:
konstantina@wustl.edu
Investigator:
Last name:
Hiram Gay
Email:
Principal Investigator
Facility:
Name:
Dayton Physicians
Address:
City:
Kettering
Zip:
45409
Country:
United States
Status:
Recruiting
Contact:
Phone:
937-771-2287
Investigator:
Last name:
Trevor Bluemel
Email:
Principal Investigator
Facility:
Name:
Oregon Urology Institute
Address:
City:
Springfield
Zip:
97477
Country:
United States
Status:
Recruiting
Contact:
Last name:
Victoria Evans
Phone:
541-284-5508
Email:
vevans@oregonurology.com
Investigator:
Last name:
Bryan Mehlhaff
Email:
Principal Investigator
Facility:
Name:
Carolina Urologic Research Center, LLC
Address:
City:
Myrtle Beach
Zip:
29572
Country:
United States
Status:
Recruiting
Contact:
Last name:
Katie Valipour
Phone:
843-839-1679
Email:
kvalipour@curcmb.com
Investigator:
Last name:
Neal D Shore
Email:
Principal Investigator
Facility:
Name:
Virginia Oncology Associates .
Address:
City:
Norfolk
Zip:
23502
Country:
United States
Status:
Recruiting
Contact:
Last name:
Teri Raymond
Phone:
757-466-8683
Email:
teri.raymond@usoncology.com
Investigator:
Last name:
Mark Fleming
Email:
Principal Investigator
Facility:
Name:
Novartis Investigative Site
Address:
City:
Darlinghurst
Zip:
2010
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Malvern
Zip:
3144
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Linz
Zip:
4020
Country:
Austria
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Wien
Zip:
1090
Country:
Austria
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Gent
Zip:
9000
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Wilrijk
Zip:
2610
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Montreal
Zip:
H2X 1R9
Country:
Canada
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Montreal
Zip:
H3T 1E2
Country:
Canada
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Quebec
Zip:
G1J 1Z4
Country:
Canada
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Olomouc
Zip:
779 00
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Ostrava
Zip:
708 52
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Praha 5
Zip:
150 06
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Saint-Cloud
Zip:
92210
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bron
Zip:
69677
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Clermont-Ferrand
Zip:
63011
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Rouen
Zip:
76038
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Saint Herblain
Zip:
44805
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Debrecen
Zip:
4032
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Beer Sheva
Zip:
8457108
Country:
Israel
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Haifa
Zip:
3109601
Country:
Israel
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Jerusalem
Zip:
9112001
Country:
Israel
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Petach Tikva
Zip:
4941492
Country:
Israel
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Tel Aviv
Zip:
6423906
Country:
Israel
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Milano
Zip:
20141
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Kashiwa
Zip:
277 8577
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Fukuoka city
Zip:
812-8582
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Fukushima city
Zip:
960 1295
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Sapporo city
Zip:
060 8648
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Kobe
Zip:
650-0047
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Kanazawa
Zip:
920 8641
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Yokohama-city
Zip:
236-0004
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Fukuoka
Zip:
811-0213
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Fukuoka
Zip:
812-0033
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Kyoto
Zip:
606 8507
Country:
Japan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Singapore
Zip:
119228
Country:
Singapore
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Singapore
Zip:
168583
Country:
Singapore
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bratislava
Zip:
83310
Country:
Slovakia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Kosice
Zip:
041 91
Country:
Slovakia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Granada
Zip:
18014
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
El Palmar
Zip:
30120
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Geneve 14
Zip:
1211
Country:
Switzerland
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Luzern
Zip:
6006
Country:
Switzerland
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Taipei
Zip:
103616
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Taipei
Zip:
11217
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Taoyuan
Zip:
33305
Country:
Taiwan
Status:
Recruiting
Start date:
March 12, 2024
Completion date:
July 9, 2030
Lead sponsor:
Agency:
Novartis Pharmaceuticals
Agency class:
Industry
Source:
Novartis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05939414
