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

Launched by CENTRE JEAN PERRIN · Sep 13, 2024

Keywords

ClinConnect Summary

This clinical trial is studying how certain molecular markers in tumor DNA can help predict how well a treatment called 177Lutetium-PSMA-617 (Lu-PSMA) will work for men with advanced prostate cancer that no longer responds to hormone therapy. While Lu-PSMA has shown promise in improving survival rates, about 40% of patients do not benefit from it. Researchers believe that by identifying specific markers in tumor tissue, they can better determine which patients are likely to respond to this treatment.

To participate in the trial, men over 18 years old with confirmed metastatic castration-resistant prostate cancer (mCRPC) may be eligible if they have already received certain prior treatments, including at least one type of chemotherapy and a second-generation hormone therapy. Participants will provide samples of their tumor tissue for analysis. Throughout the study, they can expect regular check-ups to monitor their health and response to the treatment. This trial aims to improve personalized treatment options for patients with mCRPC by finding reliable methods to predict treatment outcomes.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• • 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
• * 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.
• * Patients with at least one metastasis, bone and/or soft tissue and/or visceral, documented by the following methods in the 28 days prior to randomization :
• • 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 1.5 cm 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. PET 68Ga-PSMA-11 positive lesions defined as :
• • Any lesion with a higher hypermetabolism than the hepatic parenchyma
• • A lymph node lesion of more than 2.5cm of small axis
• • Bone metastases with soft tissue component ≥ 10 mm in largest diameter
• • Metastases of solid organs (for example, lung, liver, adrenal glands, etc.) ≥ 10 mm in the largest diameter.
• * Adequate organ function :
• * Bone marrow reserve :
• • Absolute neutrophil count ≥ 1.5 x 10\^9/L
• • Platelets ≥ 100 x 10\^9/L.
• • Hemoglobin ≥ 9 g/dL
• * Hepatic function :
• • Total bilirubin ≤ 2 x the upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted.
• • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastases.
• • Albumin \> 2.5 g/dL
• • Renal function : Glomerular Filtration Rate (GFR) ≥ 50 mL/min/1.73m2 according to MDRD equation.
• • Obtaining the patient's free and informed consent
• • Social security scheme or beneficiary.
• Exclusion Criteria :
• • 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
• • Concurrent participation in a therapeutic trial and administration of any investigational agent within 28 days of inclusion
• • Metastatic tumor tissue as the only material available for prostate cancer diagnosis
• • Previous treatment with any of the following in the 6 months prior to randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-cyclic irradiation
• • Previous treatment with radioligands targeting PSMA
• • Known hypersensitivity to one of the study treatments or its excipients or similar class drugs
• • Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for inclusion in the study