Study evaluating whether giving 177Lu-PSMA-617 to men having a spreading prostate cancer which does not respond well to the current standards of care could help better control the disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

4 Sep 2024 → ongoing

Decision date (initial)

2026-05-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis / AAA (Advanced Accelerator Applications)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Efficacy of 177Lu-PSMA-617 administered on top of the ongoing standard systemic treatment in patients with de novo mHSPC presenting with a serum PSA level of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation for mHSPC compared to standard systemic treatment alone in terms of Overall Survival (OS) and radiographic Progression-Free Survival (rPFS).

Secondary objectives 13

1. Efficacy_Castration-Resistant Prostate Cancer Free Survival (CRPC-FS)
2. Efficacy_Prostate cancer-specific survival (PCSS)
3. Efficay_PSA response
4. Efficacy_Skeletal-related event-free survival (SRE-FS)
5. Efficacy_Time to severe urinary event (SUE)
6. Efficacy_Time to initiation of subsequent (first and second) anti-cancer systemic therapy for CRPC
7. Efficacy of subsequent (first and second) anti-cancer systemic therapy for CRPC
8. Efficacy_Quality of life
9. Safety_Toxicity
10. Exploratory_Biomarkers correlation to disease outcomes
11. Exploratory_Early PSMA PET evaluation and correlation between PSA and PSMA uptake variation
12. Eploratory_Identification of PSMA PET imaging biomarkers to predict response and disease outcome
13. Exploratory_Radiation dosimetry of tumor tissues and normal organs to predict response and toxicity respectively

Conditions and MedDRA coding

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 (i.e. poor responders) in the absence of evidence of cancer progression (including a rising PSA level)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 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.
2. Aged ≥ 18 years old
3. Life expectancy > 6 months as per investigator estimate
4. ECOG performance status ≤ 2
5. Men with histologically or cytologically confirmed adenocarcinoma of the prostate
6. 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
7. Measurable disease or bone lesions evaluable according to PCWG3 criteria. Patients with doubtful metastases are not eligible
8. 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.
9. 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.
10. Stable or declining PSA level but not a rising one
11. Serum PSA of ≥ 0.2 ng/mL at 6 to 8 months after ADT initiation
12. Testosterone level < 50 ng/dl or < 1.7 nmol/L
13. 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)
14. 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.
15. Affiliated to the social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).
16. 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 12

1. Any evidence of cancer progression (including a rising PSA level, clinical progression, or radiological progression)
2. Prior or concurrent PSMA-based radioligand therapy or other PSMA target treatments
3. Known hypersensitivity to the components of the study therapy or its analogs
4. Any condition preventing the use of the standard of care and/or specific experimental treatments tested in the trial
5. 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
6. Hypertension not controlled by an anti-hypertensive treatment (systolic blood pressure [sBP] ≥ 160 mmHg or diastolic blood pressure [dBP] ≥ 95 mmHg)
7. Severe or uncontrolled concurrent disease, infection or co-morbidity
8. Pathological findings consistent with small cell carcinoma of the prostate
9. History of malignancy within the previous 3 years of inclusion with the exception of successfully treated basal or squamous cell skin carcinoma
10. 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..
11. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
12. Persons deprived of their liberty or under protective custody or guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall Survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. Patients still alive at time of the analysis will be censored at the date of last news.
2. Radiographic Progression-free survival (rPFS) is defined as the time from randomization to the date of radiographic progression according to PCWG3 criteria by investigator assessment, or death, whichever occurs first. In absence of radiographic progression or death, the data will be censored at the date of the last PCWG3 radiographic assessment.

Secondary endpoints 13

1. Efficacy_Castration-Resistance Prostate Cancer-Free Survival (CRPC-FS) is defined as the time from randomization to the onset of castration-resistant prostate cancer or death from any cause, whichever occurs first. In absence of castration-resistance or death, the data will be censored at the date of the last PCWG3 assessment (minimum date PSA/imaging).
2. Efficacy_Prostate cancer-specific survival (PCSS) is defined as the time from the date of randomization to the date of death due to prostate cancer. Death due to another cause than prostate cancer will be censored at the date of death. Patients still alive at time of the analysis will be censored at the date of last news.
3. Efficacy_PSA response will be assessed by the maximum change of PSA (rise or fall) from baseline over the treatment period. A complete PSA response is defined by an undetectable level of serum PSA.
4. Efficacy_Skeletal-related event-free survival (SRE-FS) is defined as the time from the randomization date to the date of diagnosis of either an SRE (fracture, or a bone pain requiring radiation therapy, or a spinal cord compression, or a preventive surgery to the bones) or death, whichever occurs first. Events will be evaluated by the investigators. No systematic X-Ray will be performed. In absence of SRE or death, data will be censored at the date of last news.
5. Efficacy_Time to severe urinary event (SUE) is defined as the time from the randomization date to the date of diagnosis of either one of the following SUE, whichever occurs first: urinary retention with need for a urinary catheter, suprapubic catheter, double J stent, nephrostomy, treatment of the prostate by radiotherapy or trans-urethral resection of the prostate or prostatectomy done to relieve patients with local symptoms. In absence of SUE, data will be censored at the date of last news.
6. Efficacy_Time to initiation of subsequent(first and second)anti-cancer systemic therapy for CRPC(TTSST1 and TTSST2).TTSST1 is defined as the time from randomization date to the date of initiation of first anti-cancer systemic therapy for CRPC.TTSST2 is defined as the time from the randomization date to the date of initiation of the second anti-cancer systemic therapy for CRPC. In absence of initiation of a subsequent anti-cancer systemic therapy, data will be censored at the date of last news
7. Efficacy of subsequent (first and second) anti-cancer systemic therapy for CRPC will be assessed by either PSA response or rPFS, or OS and will be defined as the time from first and second anti-cancer systemic therapy for CRPC to disease progression or death from any cause, whichever comes first.
8. Efficacy_Quality of Life (QoL) will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF) and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.
9. Safety_Toxicity will be evaluated according to NCI-CTCAE v5.0.
10. Exploratory_Biomarkers assessment to identify molecular characteristics and genetic or phenotypic abnormalities to correlate with disease outcome.
11. Exploratory_Early PSMA PET evaluation and correlation between PSA and PSMA uptake variation will be assessed at 3 months (after cycle 2) according to PROMISE 2.0 criteria. In case of progression detected at early PSMA PET scan, it would not be considered for stopping treatment.
12. Exploratory_Identification of PSMA PET imaging biomarkers to predict response and disease outcome will be assessed at pre-randomization based on semiquantitative analysis and total tumoral volume expressing PSMA.
13. Exploratory_Radiation dosimetry of tumor tissues and normal organs (notably in salivary gland, bone marrow and kidney) to predict response and toxicity respectively will be perfomed on post-therapeutic images performed after the first cycle of 177Lu PSMA-617 (at least at 4 hours for output patients or 4 hours and 24 hours and Day 5 in case of hospitalization)._

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Director of Regulatory Affairs, Quality and Pharmacovigilance

Public contact point

Organisation

Unicancer

Contact name

Director of Regulatory Affairs, Quality and Pharmacovigilance

Locations

6 EU/EEA countries · 51 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications