Study comparing Lutetium (177Lu) Vipivotid-Tetraxetan (AAA617) with observation in PSMA-positive oligometastatic prostate cancer.

Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Malaysia, Netherlands, Puerto Rico, Singapore, Slovakia, Spain, Switzerland, Taiwan, United Kingdom, United States (ICTRP)

ICTRP Trial ID
NCT05939414 (ICTRP)

Official title (approved by ethics committee)
An International, Prospective, Open-label, Multi-center, Randomized Phase III Study comparing lutetium (177Lu) vipivotide tetraxetan (AAA617) versus observation to delay castration or disease recurrence in adult male patients with prostate-specific membrane antigen (PSMA) positive Oligometastatic Prostate Cancer (OMPC). (BASEC)

Academic title
An International, Prospective, Open-label, Multi-center, Randomized Phase III Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) Versus Observation to Delay Castration or Disease Recurrence in Adult Male Patients With Prostate-specific Membrane Antigen (PSMA) Positive Oligometastatic Prostate Cancer (OMPC) (ICTRP)

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

Disease under investigation
Oligometastatic Prostate Cancer (OMPC) (ICTRP)

Intervention under investigation
Drug: AAA617 (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion 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 (EBRT), (prostate
alone or prostate with seminal vesicle and/or pelvic nodes) and/or brachytherapy
prior to randomization. Biochemical recurrence (BCR) 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 1-5 PSMA -positive metastatic lesions on screening
PSMA PET/CT scan (with either gallium (68Ga) gozetotide or piflufolastat (18F)) as
visually assessed by BIRC. For definition of PSMA PET positivity, 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 American Joint Committee on Cancer
(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 must be a distant metastasis (M1) per AJCC8
classification at screening. For AJCC M staging, PSMA PET/CT information should be
used

5. Participants must have a negative CI 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 CI 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/CT 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 CI 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 must 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) and ARPIs used for metastatic prostate
cancer treatment

- Participants who received AR-directed therapy, whether ADT or an ARPI or
both, as neoadjuvant or adjuvant therapy as a component of their primary
therapy, are eligible provided that they discontinued therapy =12 months
prior to randomization for ADT (i.e., 12 months after the last day of the
last injection) or =3 months if ARPI was given as monotherapy. ARPI's as a
term includes both contemporary androgen synthesis inhibitors (e.g.,
abiraterone, galeterone, and orteneronel), and receptor inhibitors
(enzalutamide, apalutamide and darolutamide).

- Patients who biochemically relapsed after primary therapy may also have
had treatment with AR directed therapy and participants who had SBRT with
ADT are also eligible provided that the ARPI +/- ADT or ADT alone was
terminated

=12 months prior to randomization for ADT (i.e., 12 months after the last
day of the last injection) or =3 months if ARPI was given as monotherapy.

- Participants who received first generation anti-androgens (bicalutamide,
flutamide, nilutamide, cyproterone) for biochemical recurrence or
adjuvant/neoadjuvant therapy are eligible provided that they discontinued
therapy =3 months prior to randomization.

- Participants who have discontinued ADT due to disease progression are not
eligible (i.e., Castration-Resistant Prostate Cancer (CRPC) participants)

2. Other hormonal therapy. e.g.,

Use of estrogens, 5-a 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 =3 months
before randomization.

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 participant (ICTRP)

not available

Primary and secondary end points
Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS) (ICTRP)

Key secondary endpoint: Time to Hormonal Therapy (TTHT);Investigator assessed Metastasis Free Survival (MFS);Time to prostate specific antigen (PSA) progression (TTPSAP);Radiographic Progression Free Survival (rPFS);Time to next therapy (local or systemic);24-month prostate-specific antigen (PSA) progression free survival (PFS);Time to symptomatic progression;Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire;Functional Assessment of Cancer Therapy - Radionuclide Therapy (FACT-RNT) Questionnaire;Brief Pain Inventory - Short Form (BPI-SF) Questionnaire;European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L);Time to First Symptomatic Skeletal Event (TTSE);Incidence and severity of adverse events (AEs) and serious adverse events (SAEs);Dose modifications and intensity for AAA617;Overall survival (OS) (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Novartis Pharmaceuticals;Novartis Pharmaceuticals, novartis.email@novartis.com, 1-888-669-6682, Novartis Pharmaceuticals, (ICTRP)

Secondary trial IDs
2022-502956-29-00, CAAA617D12302 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT05939414 (ICTRP)