Clinical trial NCT06060652: Prostate Oligometastatic Cancer Management Driven by Disease Biology et/or Immunoactivity (PROMETEO)
Official title: Prostate Oligometastatic Cancer Management Driven by Disease Biology et/or Immunoactivity (PROMETEO)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Oligometastatic Prostate Cancer
Lead sponsor: Centro di Riferimento Oncologico - Aviano
Sponsor class: OTHER
First posted: 2023-09-29
Enrollment: 104
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: OMPC patients undergoing SBRT

Brief summary: Currently, despite the advent of next-generation imaging has improved the detection of Oligometastatic prostate cancer (OMPC), prognostic biomarkers able to stratify patients and monitor treatment response are lacking and urgently needed. Mounting evidence suggests that molecular profiling of the disease and host immune activity evaluation can reveal OMPC heterogeneity and address the above unmet clinical need.

This study aims at combining the analysis of several biomarkers to improve the prognostic stratification of OMPC patients

Detailed description: Currently, despite the advent of next-generation imaging has improved the detection of Oligometastatic prostate cancer (OMPC), prognostic biomarkers able to stratify patients and monitor treatment response are lacking and urgently needed. Mounting evidence suggests that molecular profiling of the disease and host immune activity evaluation can reveal OMPC heterogeneity and address the above unmet clinical need.

Liquid biopsy, defined as the sampling and analysis of tumor-derived analytes \[i.e.: circulating tumor cells (CTCs), or circulating tumor DNA (ctDNA)\] from blood, represents a powerful tool to assess in real-time the evolving landscape of cancer, identify prognostic and predictive biomarkers and detect resistance to therapies in several cancers, including Prostate Cancer (PC).

Additionally, the same blood sample allows the profiling of tumor-associated components, such as circulating immune cells, which may give clues at the systemic level about the dynamic and complex host-tumor interaction. It is non-invasive, easily repeatable, and cost-effective. In this regard, preliminary results derived from clinical studies indicate that the analysis of tumor material circulating in peripheral blood, combined with the study of the host immune response might be pivotal. This study aims at combining the analysis of several biomarkers, associated with both tumor (CTC and cfDNA) and host (TCR), with a micro-invasive approach, such as liquid biopsy, to improve the prognostic stratification of OMPC patients compared to conventional laboratory test (PSA) and imaging exams (Choline- or PSMA-PET imaging).

Eligibility criteria: Inclusion criteria

Retrospective cohort

* \>18 years old;
* Patients previously included in the ADAPT-CTC trial
* Signing written informed consentInclusion Criteria:

Prospective cohort

* \>18 years old
* Histologic confirmation (primary or metastatic tumor) of Acinar Adenocarcinoma of Prostate
* Hormone-sensitive OMPC defined as ≤3 metachronous metastases (bone and/or lymph node) detected within the past 6 months with Choline/PSMA PET-CT following prostate specific antigen (PSA) rising after primary treatment (surgery and/or radiotherapy) with curative intent as defined by European Association of Urology criteria (EAU).
* Controlled primary tumor
* Prior salvage treatment to the primary prostate cancer is allowed.
* PSA ≤ 50 ng/mL
* Testosterone ≥ 0.5 ng/mL
* ADT associated to the primary treatment concluded more than 6 months prior to the enrollment.
* Patients eligible for a course of SBRT on bone and/or lymph node metastatic sites
* Patients must have a life expectancy ≥ 12 months and an ECOG performance status ≤ 2
* Patients must have normal organ and marrow function defined as:

  * Leukocytes ≥2000/µL
  * Absolute Neutrophil Count ≥1000/µL
  * Platelets ≥50000/µL
* Patients amenable to understand and sign written informed consent documents

Exclusion Criteria:

Prospective cohort

* Spinal cord compression or impending spinal cord compression.
* Suspected pulmonary and/or liver metastases
* Patient receiving any other investigational agents
* Patient is participating in a concurrent treatment protocol
* Prior treatments for hormone-sensitive OMPC
* Serum creatinine \> 3 times the upper limit of normal.
* Total bilirubin \> 3 times the upper limit of normal.
* Liver Transaminases \> 5-times the upper limit of normal.
* Unable to lie flat during or tolerate PET/CT or SBRT.
* Previous history of cancer other than non-melanoma skin cancer in the last 5 years
* Traumatic bone events in the 4 weeks before PET

Primary outcomes:
measure: Validation of the prognostic significance of CTCs in a prospective cohort of OMPC patients undergoing SBRT
timeFrame: up to 3 years
Secondary outcomes:
measure: Biochemical-PSF and CTC
timeFrame: up to 3 years
measure: Biochemical-PSF and TCR
timeFrame: up to 3 years
measure: Identify signatures in cfDNA of prognostic significance in terms of Biochemical-PSF
timeFrame: up to 3 years
measure: Distant-PSF and CTC
timeFrame: up to 3 years
measure: Distant-PSF and TCR
timeFrame: up to 3 years
measure: Identify signatures in cfDNA of prognostic significance in terms of Distant-PSF
timeFrame: up to 3 years
measure: Local control and CTC
timeFrame: up to 3 years
measure: Local control and TCR
timeFrame: up to 3 years
measure: Identify signatures in cfDNA of prognostic significance in terms of Local control
timeFrame: up to 3 years
measure: ADT-free survival and CTC
timeFrame: up to 3 years
measure: ADT-free survival and TCR
timeFrame: up to 3 years
measure: Identify signatures in cfDNA of prognostic significance in terms of ADT-free survival
timeFrame: up to 3 years
measure: time to castration resistant Prostate Cancer and CTC
timeFrame: up to 3 years
measure: time to castration resistant Prostate Cancer and TCR
timeFrame: up to 3 years
measure: Identify signatures in cfDNA of prognostic significance in terms of time to castration resistant Prostate Cancer
timeFrame: up to 3 years
measure: Overall survival and CTC
timeFrame: up to 3 years
measure: Overall survival and TCR
timeFrame: up to 3 years
measure: Identify signatures in cfDNA of prognostic significance in terms of Overall survival
timeFrame: up to 3 years
measure: TCR values
timeFrame: up to 3 years
measure: cfDNA
timeFrame: up to 3 years
measure: prognostic value of the combination of different biomarkers
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: IRCCS-Centro di Riferimento Oncologico (CRO) di Aviano
state: Pordenone
city: Brescia
country: Italy
facility: ASST Spedali Civili
Study officials:
affiliation: Centro di Riferimento Oncologico (CRO), IRCCS
name: Fabio Matrone, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro di Riferimento Oncologico di Aviano (CRO)
name: Giulia Brisotto, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro di Riferimento Oncologico di Aviano (CRO)
name: Matteo Turetta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro di Riferimento Oncologico di Aviano (CRO)
name: Fabio Del Ben, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Asst Degli Spedali Civili Di Brescia
name: Luca Triggiani, MD
role: PRINCIPAL_INVESTIGATOR
References: