Ignite Creation Date:
2024-05-06 @ 3:24 PM
Last Modification Date:
2024-10-26 @ 1:49 PM
Study NCT ID:
NCT04624828
Status:
RECRUITING
Last Update Posted:
2023-02-06
First Post:
2020-11-02
Brief Title:
Immune Response Evaluation in Oligorecurrent and Oligoprogressive Prostate Cancer Patients Treated With SBRT
Sponsor:
Istituto Clinico Humanitas
Organization:
Istituto Clinico Humanitas
Study Overview
Official Title:
Pilot Study of Immune Response Evaluation in Oligorecurrent and Oligoprogressive Prostate Cancer Patients Treated With Metastases-directed Stereotactic Body Radiation Therapy SBRT With and Without Concomitant Androgen Deprivation Therapy
Status:
RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IOSCAR
Brief Summary:
At the moment there is a lack of data in the setting of oligometastatic PC in particular regarding the interaction between ablative SBRT ADT and patients immune system response
The hypothesis underlying this project consists in the idea that the patients immunological context RT and ADT may interact in the context of metastatic PC Indeed the immune landscape of patients may interfere with the efficacy of SBRT and on the other side RT may modulate the immune response by driving immunotolerance
Scope of the study will be to investigate the immune modulation after SBRT in
patients with diagnosis of oligorecurrence during a treatment-free interval
patients with oligoprogression or oligopersistance during hormonal therapy
The hypothesis underlying this project consists in the idea that the patients immunological context RT and ADT may interact in the context of metastatic PC Indeed the immune landscape of patients may interfere with the efficacy of SBRT and on the other side RT may modulate the immune response by driving immunotolerance
Scope of the study will be to investigate the immune modulation after SBRT in
patients with diagnosis of oligorecurrence during a treatment-free interval
patients with oligoprogression or oligopersistance during hormonal therapy
Detailed Description:
Prostate cancer PC represents the second most common cancer in men worldwide managed with surgery or radiotherapy RT in case of localized disease
Advanced PC can metastasize and often presents as an oligometastatic state defined as an intermediate state between localized and widespread diffused disease Oligometastatic PC is characterized by the presence of a limited number of metastases commonly 1 to 5 lesions Recently the ESTRO-EORTC collaboration characterized the oligometastatic disease and provided a classification into oligorecurrence and oligoprogression considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy
Most common sites of metastases from PC are bones and lymph nodes Different studies have been already published for oligometastatic PC patients Singh et al reported that a number of metastases limited to 5 developed during follow-up after curative treatment of primary tumor is significantly associated to a better 5-year survival rate 73 vs 43 of patients with more than 5 metastases
In case of limited number of metastases stereotactic body radiation therapy SBRT seems to be effective but its role in the management of metastatic PC is still debated due to the paucity of prospective and randomized trials
We reported the outcome of 92 oligometastatic PC patients treated with SBRT reaching 1 and 3 years control of treated lesions in 909 95CI 818 - 956 and 855 95CI 744 - 920 and a median overall survival of 916 months
Ost et al conducted a randomized trial comparing surveillance versus metastases directed therapy in a sample of 62 hormone naïve metastatic PC patients With a median follow-up time of 3 years the median ADT-free survival was 13 months for surveillance group versus 21 for the treatment group In terms of PFS the median time until progression was 6 months for the surveillance group as compared with 10 months for the MDT group p 003
Main benefits from SBRT in oligometastatic setting are potentially the increasing time of freedom from systemic therapy in naïve patients the delay of the intensification of systemic therapy in patients already under treatment Moreover another relevant advantage from SBRT is the ability to modulate the tumor immune microenvironment as showed by preliminary studies In particular SBRT has been shown to induce immune responses in treated patients with potentially improved tumor control
RT is able to elicit a potent anti-tumour immune response driven by the activation of T cells infiltrating the tumor and the increase of antigen-presenting cell cross-presentation and on the other hand also seems to enhance immunosuppression in cancer mainly mediated by the recruitment and activation of anti-inflammatory and pro-tumorigenic myeloid cell subsets The immune landscape of patients may interfere with the efficacy of radiation therapy and on the other side SBRT may modulate the immune response by driving immuno-tolerance
The impact of RT may vary depending on tumor type and time of delivery In addition the immune modulation determined by RT may depend on the dose per fraction On this regard ablative dose of fractionated radiations were shown to elicit an anti-tumorigenic response mediated by T cell activation in a model of breast cancer that was not observed at conventional doses So far no relevant studies have been published regarding the role of SBRT in the immune modulation of metastatic PC patients Neither the combination of SBRT and androgen deprivation has been explored prospectively in terms of immune response This however is an area of interest considering that preclinical studies showed that hormonal therapy seems to increase the numbers of circulating naive T cells shortly after beginning of ADT and decrease numbers of circulating CD4 Treg At the same time infiltrating myeloid subsets have been reported to facilitate resistance to ADT in mouse models of PC
At the moment there is a lack of data in the setting of oligometastatic PC in particular regarding the interaction between ablative SBRT ADT and patients immune system response
The hypothesis underlying this project consists in the idea that the patients immunological context RT and ADT may interact in the context of metastatic PC Indeed the immune landscape of patients may interfere with the efficacy of SBRT and on the other side RT may modulate the immune response by driving immunotolerance
Scope of the study will be to investigate the immune modulation after SBRT in
patients with diagnosis of oligorecurrence during a treatment-free interval
patients with oligoprogression or oligopersistance during hormonal therapy
Advanced PC can metastasize and often presents as an oligometastatic state defined as an intermediate state between localized and widespread diffused disease Oligometastatic PC is characterized by the presence of a limited number of metastases commonly 1 to 5 lesions Recently the ESTRO-EORTC collaboration characterized the oligometastatic disease and provided a classification into oligorecurrence and oligoprogression considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy
Most common sites of metastases from PC are bones and lymph nodes Different studies have been already published for oligometastatic PC patients Singh et al reported that a number of metastases limited to 5 developed during follow-up after curative treatment of primary tumor is significantly associated to a better 5-year survival rate 73 vs 43 of patients with more than 5 metastases
In case of limited number of metastases stereotactic body radiation therapy SBRT seems to be effective but its role in the management of metastatic PC is still debated due to the paucity of prospective and randomized trials
We reported the outcome of 92 oligometastatic PC patients treated with SBRT reaching 1 and 3 years control of treated lesions in 909 95CI 818 - 956 and 855 95CI 744 - 920 and a median overall survival of 916 months
Ost et al conducted a randomized trial comparing surveillance versus metastases directed therapy in a sample of 62 hormone naïve metastatic PC patients With a median follow-up time of 3 years the median ADT-free survival was 13 months for surveillance group versus 21 for the treatment group In terms of PFS the median time until progression was 6 months for the surveillance group as compared with 10 months for the MDT group p 003
Main benefits from SBRT in oligometastatic setting are potentially the increasing time of freedom from systemic therapy in naïve patients the delay of the intensification of systemic therapy in patients already under treatment Moreover another relevant advantage from SBRT is the ability to modulate the tumor immune microenvironment as showed by preliminary studies In particular SBRT has been shown to induce immune responses in treated patients with potentially improved tumor control
RT is able to elicit a potent anti-tumour immune response driven by the activation of T cells infiltrating the tumor and the increase of antigen-presenting cell cross-presentation and on the other hand also seems to enhance immunosuppression in cancer mainly mediated by the recruitment and activation of anti-inflammatory and pro-tumorigenic myeloid cell subsets The immune landscape of patients may interfere with the efficacy of radiation therapy and on the other side SBRT may modulate the immune response by driving immuno-tolerance
The impact of RT may vary depending on tumor type and time of delivery In addition the immune modulation determined by RT may depend on the dose per fraction On this regard ablative dose of fractionated radiations were shown to elicit an anti-tumorigenic response mediated by T cell activation in a model of breast cancer that was not observed at conventional doses So far no relevant studies have been published regarding the role of SBRT in the immune modulation of metastatic PC patients Neither the combination of SBRT and androgen deprivation has been explored prospectively in terms of immune response This however is an area of interest considering that preclinical studies showed that hormonal therapy seems to increase the numbers of circulating naive T cells shortly after beginning of ADT and decrease numbers of circulating CD4 Treg At the same time infiltrating myeloid subsets have been reported to facilitate resistance to ADT in mouse models of PC
At the moment there is a lack of data in the setting of oligometastatic PC in particular regarding the interaction between ablative SBRT ADT and patients immune system response
The hypothesis underlying this project consists in the idea that the patients immunological context RT and ADT may interact in the context of metastatic PC Indeed the immune landscape of patients may interfere with the efficacy of SBRT and on the other side RT may modulate the immune response by driving immunotolerance
Scope of the study will be to investigate the immune modulation after SBRT in
patients with diagnosis of oligorecurrence during a treatment-free interval
patients with oligoprogression or oligopersistance during hormonal therapy
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