A Randomized Controlled Trial Evaluating the Efficacy of Lutetium (177Lu) Vipivotide Tetraxetan in Patients with Metastatic Hormone-Sensitive Prostate Cancer Receiving Androgen Deprivation Therapy

Trial ID: 2025-522145-21-00
Protocol: PR12
Sponsor: University College London

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Diseases & Conditions

Hormone-dependent prostate cancer

Objectives

The primary objective is to evaluate whether the addition of investigational treatments to the standard of care improves survival or cancer outcomes in patients with metastatic hormone-sensitive prostate cancer initiating long-term androgen deprivation therapy. Scope: 5.

Secondary objectives include the assessment of:

Toxicity and patient compliance within the research arms.
Changes in quality of life resulting from the addition of research therapies.
Impact on treatment pathway cost and resource use.

Participants

This study involves 2,914 male participants diagnosed with metastatic hormone-sensitive prostate cancer. The study population consists of adults within specific age categories 3 and 4. Eligible subjects must have histological confirmation of prostate adenocarcinoma or strong clinical suspicion with a plan for formal diagnosis. Participants must exhibit metastatic involvement in the bone, non-regional lymph nodes, or visceral organs, as confirmed by CT, MRI, or PET imaging. The clinical presentation must be de novo or relapsed with documented hormone sensitivity. Inclusion requires the initiation of long-term androgen deprivation therapy for a minimum of two years. Participants are required to have a WHO performance status of 0–2, or a status of 3 if expected to improve due to metastatic burden. The primary objectives are to evaluate whether survival or cancer outcomes can be improved by adding research treatments to the standard of care.

Plans and Procedures

This Phase III, multi-arm multi-stage randomized controlled trial evaluates the efficacy of various treatments, including lutetium (177lu) vipivotide tetraxetan, in patients with metastatic hormone sensitive prostate cancer. The primary objective is to determine if the addition of research treatments to standard of care alongside long-term androgen deprivation therapy improves overall survival. The study methodology utilizes a platform design to test multiple comparisons. Participants undergo a screening process to confirm histological diagnosis of prostate adenocarcinoma, presence of metastatic sites via CT, MRI, or PET scans, and specific clinical presentation requirements. Following successful screening and randomization, participants receive assigned interventions. The trial is expected to conclude recruitment by December 2032. Primary outcomes are measured by time from randomization to death from any cause, while secondary endpoints include failure-free survival, radiographic progression-free survival, and prostate cancer specific survival. Study involvement may be subject to early termination based on protocol-defined conditions or clinical requirements.

Treatment

The experimental treatment consists of lutetium (177Lu) vipivotide tetraxetan, provided as a solution for injection/infusion. The administration involves an intravenous route at a dosage of 7.4 GBq.

Participants receive androgen deprivation therapy as the standard-of-care treatment for metastatic prostate cancer.

Efficacy

The efficacy of the investigational treatment in patients with metastatic hormone-sensitive prostate cancer receiving androgen deprivation therapy is evaluated through several predefined endpoints. The primary outcome for the specified comparisons is overall survival, which is defined as the duration from randomization to death from any cause.

Secondary efficacy parameters include:

Failure-free survival
Radiographic progression-free survival
Prostate cancer-specific survival
Quality of life

Inclusion and Exclusion Criteria

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Inclusion Criteria

I. At least 18 years old.
II. Histological confirmation of prostate adenocarcinoma or a strong clinical suspicion of prostate cancer with a plan to confirm the diagnosis formally before any future randomisation.
III. Confirmation of metastatic site(s) on CT/MRI and either bone or PET scan. Patients with metastatic disease meeting any of the following criteria are eligible: • Metastatic disease to the bone (in any distribution). • Non-regional lymph node metastases of any size or distribution. Lymph nodes that are only visible on PET will not be eligible as sites of metastasis. Note: If lymph nodes are the only site of metastases, then at least one must be at least 1.5cm in short axis AND outside of the pelvis. • Visceral metastases of any size or distribution.
IV. Clinical presentation is: A. de novo. OR B. relapsed with; (1) continuing hormone sensitivity in the opinion of the investigator, and; (2) all hormone treatments (e.g., ADT and ARPI) will have been completed ≥2 years prior to any future randomisation into any of the comparisons, and; (3) will have received ≤3 years total of ADT at the point of randomisation into any comparison. Note: the dates will be checked again at randomisation. It is the responsibility of the investigator to account for the time between registration and randomisation into any comparison.
V. Long-term androgen deprivation therapy (ADT) has started or there is an intention to start for a minimum of 2 years.
VI. WHO Performance Status 0-2 or, if WHO Performance Status 3, deemed to be due to metastatic burden and expected to improve with ADT. Note: Improvement to WHO status 0-2 will be checked again at randomisation into any subsequent comparison.
VII. Willing and able to comply with trial treatments.
VIII. Patient has signed informed consent form for registration into the STAMPEDE2 Trial platform.
*Listed above are the general inclusion criteria into the STAMPEDE2 platform, comparison specific eligibility criteria are listed in section 4 of the Master Protocol

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Exclusion Criteria

I. Clinically and pathologically overt small cell carcinoma.
II. Metastatic brain disease or leptomeningeal disease.
III. Any active malignancies (i.e., progressing or requiring any treatment in the previous 36 months) other than prostate cancer (except non-muscle invasive bladder cancer; non-melanomatous skin cancer or a malignancy that is considered cured with minimal risk of recurrence).
IV. Any other medical condition that in the investigator's opinion means the participant is unfit or unsuitable for long-term ADT or the trial treatments in the comparison for which they are being considered.
*Listed above are the general exclusion criteria into the STAMPEDE2 platform, comparison specific eligibility criteria are listed in section 4 of the Master Protocol