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Comparing Lutetium (177Lu) vipivotide tetraxetan to observation in oligometastatic prostate cancer

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)

Phase 3 Interventional Novartis · NCT05939414

This study is testing a new treatment called lutetium (177Lu) vipivotide tetraxetan to see if it can help people with oligometastatic prostate cancer live better and longer after their previous therapy, compared to just watching their condition.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment450 (estimated)
Ages18 Years to 100 Years
SexMale
SponsorNovartis Industry-sponsored
Drugs / interventionsChemotherapy, Immunotherapy, radiation
Locations142 sites (Fayetteville, Arkansas and 141 other locations)
Trial IDNCT05939414 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of lutetium (177Lu) vipivotide tetraxetan in patients with oligometastatic prostate cancer who have experienced progression after definitive therapy. Participants will undergo baseline assessments, including PET/CT scans, and will be randomized to receive either the investigational treatment or observation following stereotactic body radiation therapy. The study aims to delay the need for androgen deprivation therapy while maintaining quality of life. It is expected to last approximately 6.5 years.

Who should consider this trial

Good fit: Ideal candidates are men with histologically confirmed oligometastatic prostate cancer and a limited number of PSMA-positive metastatic lesions.

Not a fit: Patients with extensive metastatic disease or those who have not experienced biochemical recurrence after definitive treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly delay disease progression and improve quality of life for patients with oligometastatic prostate cancer.

How similar studies have performed: Other studies have shown promise with similar approaches in treating oligometastatic prostate cancer, indicating potential for success.

Eligibility criteria

Show full 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-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 ≥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 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.

Where this trial is running

Fayetteville, Arkansas and 141 other locations

+92 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Oligometastatic Prostate CancerLutetium vipivotide tetraxetanMetastasis Free Survivalgallium gozetotidepiflufolastatprostate-specific membrane antigenDelay CastrationStereotactic Body Radiation Therapy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.