PEACE-6 Poor Responders: A randomized phase III trial evaluating the efficacy and safety of 177Lu-PSMA-617 in addition to Standard of Care (SoC) versus SoC alone in de novo metastatic hormone-sensitive prostate cancer (mHSPC) patients having a serum PSA level of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation for mHSPC.
- Trial ID
- 2022-502408-57-00
- Protocol
- UC-GTG-2301
- Sponsor
- Unicancer
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of 177Lu-PSMA-617 when administered in conjunction with standard systemic treatment in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC) who exhibit a serum PSA level of ≥ 0.2 ng/mL at 6 to 8 months following the initiation of systemic treatment. This evaluation will focus on comparing the outcomes in terms of Overall Survival (OS) and radiographic Progression-Free Survival (rPFS) against those receiving standard systemic treatment alone. The clinical relevance of this objective lies in its potential to improve survival outcomes and delay disease progression in this patient population.
Secondary objectives include assessing the efficacy in terms of Castration-Resistant Prostate Cancer Free Survival (CRPC-FS), Prostate cancer-specific survival (PCSS), PSA response, and Skeletal-related event-free survival (SRE-FS). Additionally, the study aims to evaluate the time to severe urinary event (SUE), time to initiation of subsequent anti-cancer systemic therapy for CRPC, and the efficacy of such therapies. Quality of life and safety, particularly toxicity, are also key secondary endpoints. Exploratory objectives involve the correlation of biomarkers to disease outcomes, early PSMA PET evaluation, identification of PSMA PET imaging biomarkers, radiation dosimetry, and the role of PSMA PET scans in defining disease progression.
Participants
The clinical trial involves **male** participants diagnosed with **metastatic hormone-sensitive prostate cancer (mHSPC)**, specifically those who are poor responders to systemic treatment, as indicated by a serum PSA level of ≥ 0.2 ng/mL at 6 to 8 months after treatment initiation, without evidence of cancer progression. The study population is composed of men aged 18 years and older, with a life expectancy of more than 6 months and an ECOG performance status of ≤ 2. Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and de novo metastatic disease, with measurable disease or bone lesions evaluable according to PCWG3 criteria. The trial does not include female subjects or vulnerable populations. Participants are required to have undergone 6 to 8 months of previous and ongoing standard systemic treatment for prostate cancer, which may include androgen deprivation therapy (ADT) with docetaxel, an androgen receptor signaling inhibitor, or a combination thereof, with or without radiotherapy. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy and safety of **177Lu-PSMA-617** in addition to the standard of care (SoC) versus SoC alone in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). The trial aims to assess the overall survival (OS) and radiographic progression-free survival (rPFS) in patients with a serum PSA level of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation. The trial is expected to commence recruitment in March 2024 and conclude by April 2039.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a stable or declining PSA level, adequate organ function, and a life expectancy of more than six months. Following randomization, participants will receive either the investigational treatment or the control treatment. Regular follow-up visits will be scheduled to monitor treatment efficacy and safety, including assessments of PSA response, skeletal-related events, and quality of life. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
The expected length of participant involvement is up to 24 months, depending on the treatment arm and individual response. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. Participants will be required to comply with the protocol, including treatment administration and scheduled assessments, to ensure the integrity of the trial data.
Treatment
The clinical trial involves the administration of **Pluvicto** 1,000 MBq/mL solution for injection/infusion, which contains the active substance **lutetium (177Lu) vipivotide tetraxetan**. This pharmaceutical is provided in the form of a solution for injection/infusion and is administered intravenously. The maximum daily dose is 8.14 GBq, with a total maximum dose of 8.14 GBq over a treatment period of up to 24 weeks. The active substance is a protein-based radiopharmaceutical, and its administration is monitored to ensure compliance with the dosing schedule.
**Locametz** 25 micrograms kit for radiopharmaceutical preparation, containing the active substance **gozetotide**, is also utilized in the trial. This product is prepared as a solution for injection and administered intravenously. The dosing is calculated based on body weight, with a maximum daily dose of 2.2 MBq/kg and a total maximum dose of 259 MBq. The treatment period is limited to one day, and participant compliance is closely monitored.
**Enzalutamide** is administered in the form of soft capsules, with the active substance being **enzalutamide**. The route of administration is oral, with a maximum daily dose of 160 mg and a total maximum dose of 160 mg over a treatment period of up to 120 days. Compliance with the oral dosing schedule is monitored throughout the trial.
**Apalutamide** is provided as film-coated tablets, containing the active substance **apalutamide**. This medication is administered orally, with a maximum daily dose of 240 mg and a total maximum dose of 240 mg over a treatment period of up to 120 days. Participant adherence to the dosing regimen is tracked during the study.
**Darolutamide** is also administered in the form of film-coated tablets, with the active substance being **darolutamide**. The oral administration involves a maximum daily dose of 1200 mg and a total maximum dose of 1200 mg over a treatment period of up to 120 days. Compliance with the dosing schedule is ensured through regular monitoring.
**Abiraterone acetate** is provided as tablets, with the active substance **abiraterone acetate**. This medication is taken orally, with a maximum daily dose of 1000 mg and a total maximum dose of 1000 mg over a treatment period of up to 120 days. Participant adherence to the oral dosing schedule is monitored throughout the trial.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include **Overall Survival (OS)**, defined as the time from randomization to death from any cause, and **Radiographic Progression-Free Survival (rPFS)**, which measures the time from randomization to radiographic progression or death, as per PCWG3 criteria. Secondary endpoints encompass a range of efficacy measures such as Castration-Resistance Prostate Cancer-Free Survival (CRPC-FS), Prostate Cancer-Specific Survival (PCSS), and PSA response, which will be evaluated by the maximum change in PSA levels from baseline. Additionally, Skeletal-related Event-Free Survival (SRE-FS) and Time to Severe Urinary Event (SUE) will be monitored.
Data collection will occur at specified intervals, with assessments including patient-reported outcomes using the Brief Pain Inventory-Short Form (BPI-SF) and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Exploratory endpoints will involve biomarker assessments and early PSMA PET evaluations to correlate with disease outcomes. The trial will also explore the role of PSMA PET imaging biomarkers in predicting response and disease progression. Radiation dosimetry will be performed on post-therapeutic images to predict response and toxicity. The trial is designed to provide comprehensive data on the efficacy of 177Lu-PSMA-617 in combination with standard care for patients with metastatic hormone-sensitive prostate cancer.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed a written informed consent form prior to any trial specific procedures Note: In case of physical incapacitation, a trusted representative of their choice, which is not the Investigator or sponsor, can sign on the behalf of the patients.
- Aged ≥ 18 years old
- Life expectancy > 6 months as per investigator estimate
- ECOG performance status ≤ 2
- Men with histologically or cytologically confirmed adenocarcinoma of the prostate
- De novo metastatic disease defined by clinical or radiographic evidence of metastases at diagnosis (i.e. before any treatment started). If not available, a more recent imaging can be used
- Measurable disease or bone lesions evaluable according to PCWG3 criteria. Patients with doubtful metastases are not eligible
- A pre-randomization 68Ga-PSMA-11 PET/CT scan performed within 4 weeks prior to randomization in the trial. FDG PET scan is not required for this protocol. All patients will be treated independently from the results of pre-randomization PSMA PET scan: patients with PSMA-positive or PSMA-negative disease according to PROMISE 2.0 criteria (see table below) are eligible.
- Have 6 to 8 months of previous AND ongoing standard systemic treatment for prostate cancer at the time of signing the written informed consent form, consisting in either: • ADT with docetaxel* ± radiotherapy ** • ADT with an androgen receptor signaling inhibitor (ARSI) (i.e., abiraterone (plus prednisone), or apalutamide or darolutamide or enzalutamide) ± radiotherapy ** • ADT with docetaxel* plus an ARSI (i.e. abiraterone (plus prednisone), or darolutamide, or enzalutamide) ± radiotherapy** Note: *Docetaxel must have been stopped at least 4 weeks ahead of randomization. ** Previous radiotherapy to the primary tumor and/or to the metastases is accepted as long as it was not PSMA-based and must has been completed at least 4 weeks ahead of randomization.
- Stable or declining PSA level but not a rising one
- Serum PSA of ≥ 0.2 ng/mL at 6 to 8 months after ADT initiation
- Testosterone level < 50 ng/dl or < 1.7 nmol/L
- Be fit enough for 177Lu-PSMA-617 treatment: • Adequate bone marrow function: hemoglobin ≥ 90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization), absolute neutrophil count ≥ 1.5 x109/L, platelet count >100 x109/L • Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.0 x upper limit of normal (ULN), or ≤ 5.0 x ULN in the presence of liver metastases; bilirubin < 1.5 x ULN (unless known or suspected Gilbert syndrome, then < 3 x ULN is permitted) • Adequate renal function: calculated creatinine clearance ≥ 50 ml/min (using the MDRD or CKD EPI method)
- For sexually active men with female partners of reproductive potential or with pregnant women, agreement to use a condom with another effective contraceptive method during trial participation and up to 14 weeks after study treatment completion.
- Affiliated to the social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).
- Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.
Exclusion Criteria
- Any evidence of cancer progression (including a rising PSA level, clinical progression, or radiological progression)
- Prior or concurrent PSMA-based radioligand therapy or other PSMA target treatments
- Known hypersensitivity to the components of the study therapy or its analogs
- Any condition preventing the use of the standard of care and/or specific experimental treatments tested in the trial
- Any of the following within 6 months before randomization: stroke, myocardial infraction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure New York Heart Association (NYHA) Class III or IV
- Hypertension not controlled by an anti-hypertensive treatment (systolic blood pressure [sBP] ≥ 160 mmHg or diastolic blood pressure [dBP] ≥ 95 mmHg)
- Severe or uncontrolled concurrent disease, infection or co-morbidity
- Pathological findings consistent with small cell carcinoma of the prostate
- History of malignancy within the previous 3 years of inclusion with the exception of successfully treated basal or squamous cell skin carcinoma
- Ongoing participation in another clinical trial involving an investigational product.. Treatment with any investigational product must have ended within 30 days prior to inclusion in the trial..
- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
- Persons deprived of their liberty or under protective custody or guardianship
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 01 Mar 2024 | 20 |
 France | Recruiting | 01 Mar 2024 | 300 |
 Ireland | Not Yet Recruiting | 01 Mar 2024 | 10 |
 Italy | Not Yet Recruiting | 01 Mar 2024 | 25 |
 The Netherlands | Not Yet Recruiting | 01 Mar 2024 | — |
 Spain | Not Yet Recruiting | 01 Mar 2024 | 45 |
| Netherlands | — | — | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ABIRATERONE ACETATE | Comparator | — | ORAL | 1000 | 120 | SUB31647 |
DAROLUTAMIDE | Comparator | — | ORAL | 1200 | 120 | SUB185326 |
Locametz 25 micrograms kit for radiopharmaceutical preparation | Comparator | KIT FOR RADIOPHARMACEUTICAL PREPARATION | INTRAVENOUS | 2.2 | 1 | PRD10117083 |
APALUTAMIDE | Comparator | — | ORAL | 240 | 120 | SUB189031 |
Pluvicto 1 000 MBq/mL solution for injection/infusion | Test | SOLUTION FOR INJECTION/INFUSION | INTRAVENOUS | 8.14 | 24 | PRD10117050 |
ENZALUTAMIDE | Comparator | — | ORAL | 160 | 120 | SUB77412 |