Ignite Creation Date:
2024-05-06 @ 4:06 PM
Last Modification Date:
2024-10-26 @ 2:03 PM
Study NCT ID:
NCT04873427
Status:
TERMINATED
Last Update Posted:
2023-02-15
First Post:
2021-04-28
Brief Title:
In Situ Clonal Heterogeneity in Prostatic Diagnostic Biopsies
Sponsor:
Clinica Luganese Moncucco
Organization:
Clinica Luganese Moncucco
Study Overview
Official Title:
In Situ Clonal Heterogeneity in Prostatic Diagnostic Biopsies Impact on Prostate Cancer Evolution and Clinical Outcome A Retrospective Proof of Concept Study
Status:
TERMINATED
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The results of the genomic analyses were compromised due to the low DNA concentration
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a retrospective proof of concept study which aims at reconstructing the cellular heterogeneity of the tumor in multi-needle diagnostic prostate biopsy as well as any biopsy containing potentially pre-malignant tissue to study its implications in the clinical history of the disease For each patient 2 or more samples will be prepared starting from the FFPE diagnostic material The biopsy used for assigning the Gleason score will be sequenced together with two or more of the local peri-proximal biopsies with a higher level of differentiation Samples will undergo Whole Exome Sequencing with an average coverage of 300x at the Wellcome Sanger Institute WSI Hinxton UK Sequencing data will be analysed for single nucleotide variants copy number variants and structural variants by using state-of-the-art data analysis pipeline at WSI
1 Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores 6-10 using high-coverage whole exome sequencing WES and DP-based clonal analysis
2 Characterization of the relationships between pathological differentiation Gleason score and genomics-measured heterogeneity and malignancy features
3 Assessment of clinical implications of clonal heterogeneity
The study will include an average of 150 prostatic diagnostic biopsies from a cohort of 20 early metastatic PC patients and 20 non-relapsingnon-metastatic patients with indolent malignant disease
1 Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores 6-10 using high-coverage whole exome sequencing WES and DP-based clonal analysis
2 Characterization of the relationships between pathological differentiation Gleason score and genomics-measured heterogeneity and malignancy features
3 Assessment of clinical implications of clonal heterogeneity
The study will include an average of 150 prostatic diagnostic biopsies from a cohort of 20 early metastatic PC patients and 20 non-relapsingnon-metastatic patients with indolent malignant disease
Detailed Description:
Prostate cancer PCa is the leading malignancy of the male population In current clinical practice diagnostic confirmation of PCa is based on image-guided multi-needle biopsy in order to capture the intrinsic biological heterogeneity of tumors and to provide a more accurate prediction of clinical outcomes However current morphology-based approaches Gleason score may not completely describe the complexity of a malignant gland Not enough is currently known on the impact of genomic heterogeneity in a poorly-differentiated prostate especially with regards to the development of an indolent versus metastatic prostate malignancy
This is a retrospective proof of concept study which aims at reconstructing the cellular heterogeneity of the tumor in multi-needle diagnostic prostate biopsy as well as any biopsy containing potentially pre-malignant tissue to study its implications in the clinical history of the disease For each patient 2 or more samples will be prepared starting from the FFPE diagnostic material The biopsy used for assigning the Gleason score will be sequenced together with two or more of the local peri-proximal biopsies with a higher level of differentiation Samples will undergo Whole Exome Sequencing with an average coverage of 300x at the Wellcome Sanger Institute WSI Hinxton UK Sequencing data will be analysed for single nucleotide variants copy number variants and structural variants by using state-of-the-art data analysis pipeline at WSI
1 Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores 6-10 using high-coverage whole exome sequencing WES and DP-based clonal analysis
2 Characterization of the relationships between pathological differentiation Gleason score and genomics-measured heterogeneity and malignancy features
3 Assessment of clinical implications of clonal heterogeneity
The study will include an average of 150 prostatic diagnostic biopsies from a cohort of 20 early metastatic PC patients and 20 non-relapsingnon-metastatic patients with indolent malignant disease
Descriptive statistics will be carried out and a Mann-Whitney test will be applied on a synthetic parameter for each patient biopsy heterogeneity result grouped by indolent vs aggressive disease cohort
The null hypotheses no difference between the two cohort in heterogeneity will be rejected if p 005
The proposed project will evaluate the impact of diagnostic intra-prostatic cell heterogeneity on the clinical course of PCa The potential prognostic value of local disease clonality could indeed impact the clinical practice patient with Gleason 7 and lower level of clonal heterogeneity may be moved from an active disease treatment to an active surveillance AS approach avoiding overtreatment for the subjects Conversely patients with a similar Gleason score but a more heterogenous malignant population may be required to undergo more aggressive procedures
This is a retrospective proof of concept study which aims at reconstructing the cellular heterogeneity of the tumor in multi-needle diagnostic prostate biopsy as well as any biopsy containing potentially pre-malignant tissue to study its implications in the clinical history of the disease For each patient 2 or more samples will be prepared starting from the FFPE diagnostic material The biopsy used for assigning the Gleason score will be sequenced together with two or more of the local peri-proximal biopsies with a higher level of differentiation Samples will undergo Whole Exome Sequencing with an average coverage of 300x at the Wellcome Sanger Institute WSI Hinxton UK Sequencing data will be analysed for single nucleotide variants copy number variants and structural variants by using state-of-the-art data analysis pipeline at WSI
1 Reconstruction of local PCa heterogeneity in multi-needle diagnostic biopsy with different Gleason scores 6-10 using high-coverage whole exome sequencing WES and DP-based clonal analysis
2 Characterization of the relationships between pathological differentiation Gleason score and genomics-measured heterogeneity and malignancy features
3 Assessment of clinical implications of clonal heterogeneity
The study will include an average of 150 prostatic diagnostic biopsies from a cohort of 20 early metastatic PC patients and 20 non-relapsingnon-metastatic patients with indolent malignant disease
Descriptive statistics will be carried out and a Mann-Whitney test will be applied on a synthetic parameter for each patient biopsy heterogeneity result grouped by indolent vs aggressive disease cohort
The null hypotheses no difference between the two cohort in heterogeneity will be rejected if p 005
The proposed project will evaluate the impact of diagnostic intra-prostatic cell heterogeneity on the clinical course of PCa The potential prognostic value of local disease clonality could indeed impact the clinical practice patient with Gleason 7 and lower level of clonal heterogeneity may be moved from an active disease treatment to an active surveillance AS approach avoiding overtreatment for the subjects Conversely patients with a similar Gleason score but a more heterogenous malignant population may be required to undergo more aggressive procedures
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None