Trial Title:
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
NCT ID:
NCT06600802
Condition:
Castration-resistant Metastatic Prostate Cancer
Treated by 177Lutetium-PSMA-617 (Lu-PSMA)
Conditions: Official terms:
Prostatic Neoplasms
Conditions: Keywords:
mCRPC
Lu-PSMA
biomarkers
response
prediction
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Blood samples
Description:
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.
Arm group label:
Interventional
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.
Detailed description:
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.
This is an interventional, multi-center study. The study is prospective, single-arm,
open-label and non-randomized.
Its primary objective is to identify biomarkers of interest, in primary tissue,
predictive of response to Lu-PSMA treatment in patients with mCRPC, through the detection
of molecular abnormalities in DNA/RNA and methyloma.
Criteria for 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
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centre Jean PERRIN
Address:
City:
Clermont-Ferrand
Zip:
63011
Country:
France
Contact:
Last name:
Judith PASSILDAS JAHANMOHAN, PhD
Phone:
0473278005
Email:
judith.passildas@clermont.unicancer.fr
Contact backup:
Last name:
Tressie HERRMANN, Dr
Facility:
Name:
CHU de Grenoble
Address:
City:
La Tronche
Zip:
38700
Country:
France
Contact:
Last name:
Loic DJAILEB, Dr
Facility:
Name:
Hospices Civiles de Lyon
Address:
City:
Pierre-Bénite
Zip:
69310
Country:
France
Contact:
Last name:
Denis MAILLET, Dr
Facility:
Name:
Hôpital privé de la Loire
Address:
City:
Saint-Étienne
Zip:
42100
Country:
France
Contact:
Last name:
Aline GUILLOT, Dr
Facility:
Name:
Institut de Cancérologie Strasbourg Europe
Address:
City:
Strasbourg
Zip:
67091
Country:
France
Contact:
Last name:
Francois SOMME, Dr
Start date:
September 30, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Centre Jean Perrin
Agency class:
Other
Collaborator:
Agency:
Groupement Inter-Régional de Recherche Clinique et d'Innovation (GIRCI) Auvergne Rhône-Alpes
Agency class:
Other
Source:
Centre Jean Perrin
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06600802
