Breast Cancer, Prostate Cancer, Pancreatic Cancer, Ovarian Cancer
Conditions
Keywords
CTC, PARPi, HR status
Brief summary
The goal of this clinical trial is to is to evaluate whether a correlation exists between functional HR status/CTC enumeration in expanded CTCs measured before treatment initiation, and Progression Free Survival (PFS) under PARPi and/or DNA-damaging. This proof-of-concept study is a first step to confirm the hypothesis that a dual parameter approach combining (i) longitudinal monitoring of CTC enumeration and (ii) functional assessment of HR capacity in ex vivo expanded CTCs will enable accurate prediction of therapeutic response to PARPi and cytotoxic chemotherapies, particularly those involving cross-linking DNA-damaging agents such as platinum salts in 300 adult patients witch advances/metastatic Ovarian, Breast, Prostate, or Pancreatic cancer potentially eligible to PARP inhibitor treatment as standards of care at the center Léon Bérard. The main questions it aims to answer are: * Correlation between functional HR status/CTC enumeration in expanded CTCs measured before treatment initiation and Progression Free Survival (PFS) under PARPi and/or DNA-damaging chemotherapy * Proportion of patients from whom ≥1 CTC colony can be successfully isolated and expanded ex vivo under predefined culture conditions * Distribution of CTC samples classified as HR-proficient vs HR-deficient based on assay-specific thresholds
Interventions
PROCEDUREblood sampling
Blood samples will be collected at 4 timepoints: prior to induction chemotherapy if applicable, prior to initiation of PARPi treatment, after 1 full cycle of PARPi (28 days) and in case of progression
PROCEDURETumor sampling
Archival FFPE tumor samples from initial diagnosis, surgery, or biopsy in case of relapse/progression will be collected if available. If a biopsy is performed during the study as part of standard of care, an additional fragment will be collected for this study.
Sponsors
Centre Leon Berard
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients ≥ 18 years at the day of signing informed consent. * Advanced/metastatic breast, prostate, ovarian and pancreatic cancer patients potentially eligible to PARP inhibitor treatment as monotherapy or in combination as per respective SmPC (see Appendix 1) or IB if the PARPi treatment is investigational. * Patients who have understood, dated, and signed the written voluntary informed consent form before undergoing any procedure specific to the protocol. * Patients affiliated with or benefiting from medical insurance.
Exclusion criteria
* Patients with secondary malignancy with the exception of basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate cancer, prior malignancy and no evidence of recurrence for ≥ 2 years. * Patients presenting a psychological, familial, geographical, or social situation that, in the investigator's judgment, could potentially prevent the signing of informed consent and/or compliance with study procedures. * Pregnant or breast-feeding women. * Patients under judicial protection (guardianship, curatorship, or legal safeguard), adults under protection in accordance with Articles L.1121-6, L.1121-8, and L.1121-8-1 of the French Public Health Code, as well asindividuals not affiliated with a social security scheme or without equivalent health coverage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between functional HR status/CTC enumeration in expanded CTCs measured before treatment initiation and Progression Free Survival (PFS) under PARPi and/or DNA-damaging chemotherapy | Until up to 18 years follow-up of the last patient enrolled | Correlation between functional HR status/CTC enumeration in expanded CTCs measured before treatment initiation and Progression Free Survival (PFS) under PARPi and/or DNA-damaging chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients from whom ≥1 CTC colony can be successfully isolated and expanded ex vivo under predefined culture conditions | Until up to 18 years follow-up of the last patient enrolled | Proportion of patients from whom ≥1 CTC colony can be successfully isolated and expanded ex vivo under predefined culture conditions |
| Distribution of CTC samples classified as HR-proficient vs HR-deficient based on assay-specific thresholds | Until up to 18 years follow-up of the last patient enrolled | Distribution of CTC samples classified as HR-proficient vs HR-deficient based on assay-specific thresholds |
| Correlation between functional HR status/CTC enumeration with response rate (RR) and OS | Until up to 18 years follow-up of the last patient enrolled | Correlation between functional HR status/CTC enumeration with response rate (RR) and OS |
Contacts
CONTACTJulie MOUILLAUX
CONTACTElise CUCHET
PRINCIPAL_INVESTIGATORMarie LAURENT, Dr
Centre Leon Berard
Outcome results
None listed