Authorised Therapeutic confirmatory (Phase III) Oligometastatic prostate cancer (OMPC)

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)

EU CTIS ID: 2022-502956-29-00

What this study is testing

To evaluate the Blinded Independent Review Committee (BIRC) assessed metastasis free survival (MFS) by conventional imaging (CI)in adult participants with OMPC defined by PSMA Positron Emission Tomography (PET) receiving AAA617 vs observation

  • Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • Histologically confirmed prostate cancer prior to randomization
  • Participants must have biochemically recurrent disease after definitive treatment to prostate by RP, (alone or with post-operative radiation to prostate bed/pelvic nodes) or 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 RT)
  • 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 the definition of PSMA PET positivity of a lesion, please refer to Section 8.1 and 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)
  • 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
  • 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 scan and one reader for CI: Reader will be blinded to PSMA PET scan results while reading CI scans. Readers 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/CT 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 are 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
  • All metastatic lesions detected at screening must be amenable to SBRT

You likely can't join if

  • 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: a. ADT (including bilateral orchiectomy) and ARPIs used for metastatic prostate cancer treatment • Participants who received AR-directed therapy, whether ADT or an AARPI 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., CRPC participants) b. Other hormonal therapy. e.g., • Use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethamide) 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 ≥3 months before randomization. c. Radiopharmaceutical agents (e.g., Strontium-89, PSMA-targeted radioligand therapy) d. Immunotherapy (e.g., sipuleucel-T) e. Chemotherapy, except if administered in the adjuvant/neoadjuvant setting completed > 12 months before randomization f. Any other investigational or systemic agents for metastatic disease
  • 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), 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
See the full eligibility criteria
Who can join
  • Histologically confirmed prostate cancer prior to randomization
  • Participants must have biochemically recurrent disease after definitive treatment to prostate by RP, (alone or with post-operative radiation to prostate bed/pelvic nodes) or 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 RT)
  • 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 the definition of PSMA PET positivity of a lesion, please refer to Section 8.1 and 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)
  • 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
  • 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 scan and one reader for CI: Reader will be blinded to PSMA PET scan results while reading CI scans. Readers 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/CT 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 are 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
  • All metastatic lesions detected at screening must be amenable to SBRT
  • Non-castration testosterone level >100 ng/dL at screening
What rules you out
  • 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: a. ADT (including bilateral orchiectomy) and ARPIs used for metastatic prostate cancer treatment • Participants who received AR-directed therapy, whether ADT or an AARPI 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., CRPC participants) b. Other hormonal therapy. e.g., • Use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethamide) 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 ≥3 months before randomization. c. Radiopharmaceutical agents (e.g., Strontium-89, PSMA-targeted radioligand therapy) d. Immunotherapy (e.g., sipuleucel-T) e. Chemotherapy, except if administered in the adjuvant/neoadjuvant setting completed > 12 months before randomization f. Any other investigational or systemic agents for metastatic disease
  • 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), 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 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.

The study team makes the final eligibility decision.

Where it's taking place

  • United States
  • Argentina
  • Brazil
  • United Kingdom
  • Australia
  • Malaysia
  • China
  • Japan
  • Singapore
  • Israel
  • Mexico
  • Canada
  • Colombia
  • Switzerland
  • Taiwan

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling male, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; Argentina; Brazil; United Kingdom; Australia; Malaysia and 9 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.