Intrinsic Validity of Molecular Marker(s) Detection on Tissular Tumoral DNA to Predict the Efficacy of 177Lutetium-PSMA-617 (Lu-PSMA) Treatment for Castration-resistant Metastatic Prostate Cancer

NCT06600802 | Recruiting

• 1 other identifier: 2024-A00246-41
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

Brief Summary

Prostate cancer is the most common cancer in men. Its incidence is rising as the population ages. In the localized stage, the 5-year overall survival rate (OS) is 98%. Metastatic progression and resistance to castration have a negative impact on prognosis. Despite recent advances in management, the 5-year OS is around 30%. Therapeutic advances in this indication have been made mainly by the use of taxanes and second-generation hormone therapy. These treatments have improved OS and progression-free survival (PFS). They are now used as standard therapy. More recently, the Phase III VISION trial confirmed the improvement in OS and radiological PFS achieved by treatment with the radioligand 177Lutetium-PSMA-617 (Lu-PSMA) in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). This treatment is currently available in early access in France. Despite encouraging results, 40% of patients will not respond to Lu-PSMA, and there are currently no validated predictive factors. Studies are currently on going, but the identification of biomarkers seems necessary to better stratify risk in these patients. Numerous tissue prognostic tests based on molecular characteristics or cell proliferation are emerging with this in mind. At present, molecular profiling is not a routine technique for prostate cancer, as it is for other solid cancers. At an early stage, the Decipher® Genomic classification tool has shown prognostic utility independently of therapeutic and clinico-pathological data. According to recent studies, methylome analysis would enable the subdivision of mCRPCs and could help identify new therapeutic targets. In the metastatic phase, certain molecular abnormalities involving DNA repair genes are predictive of response to PARP inhibitors. Molecular analysis (mutations, copy number alterations, gene expression, DNA methylation) could therefore be useful in optimizing the management of mCRPC patients treated with Lu-PSMA. If reliable molecular abnormalities are identified on tissue, a diagnostic technique based on circulating tumor DNA (ctDNA) analysis will be useful in decision-making for these patients. A biological collection will therefore be created during the course of this study, with a view to using ctDNA analysis in subsequent research.

Conditions

Treated by 177Lutetium-PSMA-617 (Lu-PSMA); Castration-resistant Metastatic Prostate Cancer

Keywords

mCRPC; Lu-PSMA; biomarkers; response; prediction

Outcome Measures

Primary Outcomes (1)

• Molecular abnormalities retained on primary tumor sample predicting response to Lu-PSMA in metastatic castration resistant prostate cancer patients assessed according to RECIST 1.1 and/or PCWG3 criteria

  Biological interpretation and response to Lu-PSMA treatment on bone scan and CT scan according to RECIST 1.1 and/or PCWG3 criteria

  From enrollment to 24 months after Lu-PSMA treatment

Secondary Outcomes (9)

• Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without radiological progression

  From enrollment to 24 months after Lu-PSMA treatment

• Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without biological progression

  From enrollment to 24 months after Lu-PSMA treatment

• Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and survival without clinical progression

  From enrollment to 24 months after Lu-PSMA treatment

• Correlation between biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and overall survival

  From enrollement to the end of the study, up to 58 months

• Correlation between the biomarker(s) (molecular abnormalities retained on primary tumor sample for the first outcome measure) and adverse effects during treatment.

  From enrollment to the end of Lu-PSMA treatment, up to 58 months

Study Arms (1)

Interventional

EXPERIMENTAL

Genetic analysis will be conducted on intial tumor sample in order to identify biomarkers

Biological: Blood samples

Interventions

Blood samples BIOLOGICAL

A total of 3 blood samples (2 tubes of 9mL each) are added. The first sample will be taken at the inclusion visit, the 2nd at the end of the 2nd treatment cycle and the last at the end of Lu-PSMA treatment.

Interventional

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male \>18 years of age
• ECOG ≤ 2
• Patient with histologically confirmed of metastatic castration resistant prostatic adenocarcinoma and with tumor biological material available (prostatic biopsies or prostatectomy)
• Patient who received at least one taxane line and a second generation hormone therapy line
• Patient receiving androgen deprivation therapy with serum testosterone \< 50 ng/dL or \< 1.7 nmol/L or having undergone surgical castration
• Progressive mCRPC based based on at least 1 of the following criteria :
• Serum or plasma PSA progression defined as 2 consecutive increases in PSA measured at least 1 week prior. The minimal start value is 2.0 ng/mL ; 1,0 ng/mL is the minimal start value if confirmed increase in PSA is the only indication of progress
• Soft-tissue progression by RECIST 1.1 criteria
• Progression of bone disease : two new lesions ; only the positivity of bone scan defines metastatic bone disease, according to PCWG3 criteria.
• Bone metastasis (regardless of location) highlighted by bone scan AND/OR
• Lymph nodes metastasis, regardless of size and location; if the metastasis are only lymph nodes, the short axis of at least one node should be at least 15 mm AND outside the pelvis ; AND/OR
• Visceral metastasis, regardless of size and location; a history of visceral metastasis at any time prior to randomization should be encoded as the presence of visceral metastasis at baseline (i.e., a patient with visceral metastasis prior ADT introduction which are disappeared at baseline will be counted as having visceral metastasis and will be considered to have a high tumor volume during stratification)
• Patient with Lu-PSMA treatment indication, confirmed by PET 68Ga-PSMA-11. Eligibility for 68Ga-PSMA-11 PET is defined as:
• At least one lesion with a binding intensity greater than that of the liver parenchyma (definition of positivity),
• All lymph node lesions larger than 25 mm in the short axis must be positive on PSMA PET

You may not qualify if:

• Continuation of second-generation hormone therapy Patient
• Other cancer in the last 3 years likely to change life expectancy or interfere with the assessment of the disease
• Protected adult
• History of somatic or psychiatric illness/condition that may interfere with study objectives and evaluations
• Patient unable to understand and comply with study instructions and requirements
• ECOG \> 2
• Dilation of pyelocalicial cavities not previously supported
• Obstruction of bladder discharge or uncontrollable and simultaneous urinary incontinence
• Symptomatic spinal cord compression or clinical or radiological findings indicating imminent spinal cord compression
• Fractured risk of bone damage
• Active and symptomatic brain injury
• Metastatic tumor tissue as the only material available for prostate cancer diagnosis
• Previous treatment with radioligands targeting PSMA
• Known hypersensitivity to one of the study treatments or its excipients or similar class drugs

Sponsors & Collaborators

• GIRCI Auvergne Rhône-Alpes: collaborator
• Centre Jean Perrin: lead

Study Sites (5)

Centre Jean PERRIN

Clermont-Ferrand, 63011, France

RECRUITING

CHU de Grenoble

La Tronche, 38700, France

NOT YET RECRUITING

Hospices Civiles de Lyon

Pierre-Bénite, 69310, France

NOT YET RECRUITING

Hôpital privé de la Loire

Saint-Etienne, 42100, France

NOT YET RECRUITING

Centre Paul STRAUSS

Strasbourg, 67091, France

NOT YET RECRUITING

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Judith PASSILDAS JAHANMOHAN, PhD

CONTACT

0473278005; judith.passildas@clermont.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: September 19, 2024
• Study Start: October 8, 2024
• Primary Completion (Estimated): June 30, 2034
• Study Completion (Estimated): June 30, 2034
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

FR (5)