Oligorecurrent and Oligoprogressive Prostate Cancer PatientsIOSCARNCT04624828
Immune Response Evaluation in Oligorecurrent and Oligoprogressive Prostate Cancer Patients Treated With SBRT
A study testing Radiotherapy, androgen deprivation therapy (ADT) and immune evaluation in people with Oligorecurrent and Oligoprogressive Prostate Cancer Patients, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial 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 patient's immune system response. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Oligorecurrent and Oligoprogressive Prostate Cancer Patients
- What is being tested?
- Radiotherapy, androgen deprivation therapy (ADT) and immune evaluation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 19 Oct 2020to Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18years
- Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
- Adenocarcinoma of the prostate treated with radical prostatectomy or radical RT
- Diagnosis of 1 to 3 metachronous metastases to bone or lymph nodes or oligoprogression / oligopersistance during ADT of a maximum of 3 metastases in bone or lymph nodes
- ECOG performance status of 0 - 1
- Informed consent.
Who cannot join
- Visceral metastases
- Evidence of spinal cord compression (radiological or clinical)
- Concurrent malignancy
- Inability to undergo RT
- History of inflammatory colitis or other active severe comorbidities
- Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications
- Life expectancy <6 months
Trial locations and contacts
1 site in 1 country.
About this study
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
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 patient's immune system response.
The hypothesis underlying this project consists in the idea that the patient's 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.
Read more
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
Read the 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 90.9% (95%CI 81.8 - 95.6) and 85.5% (95%CI 74.4 - 92.0), and a median overall survival of 91.6 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 = 0.03).
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 patient's immune system response.
The hypothesis underlying this project consists in the idea that the patient's 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
- Being tested
- Radiotherapy, androgen deprivation therapy (ADT), immune evaluation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RadiotherapyProcedure or surgery
RT treatment Schedule as for clinical practice: Stereotactic body radiation treatment (SBRT) will be delivered with image guidance (image-guided radiation therapy or IGRT) and in the form of volumetric modulated arc therapy (VMAT).
RT treatment Schedule: SBRT will be delivered in 1 to 6 fractions on bone or lymph node metastases. The dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints.
androgen deprivation therapy (ADT)Drug
ADT as for clinical practice:
- for oligorecurrent patients, ADT will be started at time of polimetastatic progression after SBRT;
- for oligoprogressive patients, ADT will be continued during SBRT and untill polimetastatic progression
immune evaluationBiological
We will use the flow cytometer FACSymphony, to analyse multiple immune populations from a limited sample of blood. We will monitor the dynamics of most innate (monocytic and granulocytic cells, Natural killer cells) and adaptive (T cells, B cells) immune subsets in the peripheral blood of PC patients before and after RT. We will deeply characterize CD4+ and CD8+ T cell subpopulations circulating in the patients enrolled in the study. In this attempt our panel will include markers of T cell differentiation and activation, including CD25, CD39, PD-1, CTL4, KLRG1, TIM3. We will analyse neutrophils subpopulations and investigate the functional profile of granulocytes in enrolled patients. Markers such as CD66b, CD24, CD16, MHC-II, LOX1, CD36 and CD62L will be included in our analysis. In conclusion our experimental strategy will result in a comprehensive profiling of the immune landscape in PC patients at single cell level.
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic body radiation treatment (SBRT) | Experimental | RT treatment Schedule as for clinical practice: Stereotactic body radiation treatment (SBRT) will be delivered with image guidance (image-guided radiation therapy or IGRT) and in the form of volumetric modulated arc therapy (VMAT).
RT treatment Schedule: SBRT will be delivered in 1 to 6 fractions on bone or lymph node metastases. The dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints. Receives: Procedure: Radiotherapy; Drug: androgen deprivation therapy (ADT); Biological: immune evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
immune evaluation
Analysis of the immunitary background performed before SBRT and evaluation of immune modulation after RT treatment. Our panels will include markers of T cell differentiation and activation, including CD25, CD39, PD-1, CTL4, KLRG1, TIM3, TIGIT. In addition we will investigate the phenotype and functional state of myeloid subsets in enrolled patients, comprising neutrophils, monocytes and dendritic cells. To this end, markers such as CD66b, CD24, CD16, MHC-II, LOX1, CD36 and CD62L will be included in our analysis.
Measured: from the baseline (before SBRT) to 7 days after the end of radiotherapy treatment
Secondary outcomes (2)
Progression free survival
Evaluation of Progression free survival (PFS)
Measured: 2 years
Prostate cancer specific survival (PCSS)
Evaluation of Prostate cancer specific survival (PCSS)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study start19 Oct 2020
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oligorecurrent and Oligoprogressive Prostate Cancer PatientsStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Collaborators
- Ipsen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04624828
- Sponsor's protocol ID
- 2683
- Acronym
- IOSCAR
- Status last verified
- Apr 2025
- First submitted
- 2 Nov 2020
- Last updated
- 24 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04624828
- Acronym / sponsor ID
- IOSCAR / 2683
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Collaborators
- Ipsen
- Study start
- 19 Oct 2020 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 12 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 patient's immune system response.
The hypothesis underlying this project consists in the idea that the patient's 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 90.9% (95%CI 81.8 - 95.6) and 85.5% (95%CI 74.4 - 92.0), and a median overall survival of 91.6 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 = 0.03).
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 patient's immune system response.
The hypothesis underlying this project consists in the idea that the patient's 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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic body radiation treatment (SBRT) | Experimental | Procedure: Radiotherapy, Drug: androgen deprivation therapy (ADT), Biological: immune evaluationRT treatment Schedule as for clinical practice: Stereotactic body radiation treatment (SBRT) will be delivered with image guidance (image-guided radiation therapy or IGRT) and in the form of volumetric modulated arc therapy (VMAT). RT treatment Schedule: SBRT will be delivered in 1 to 6 fractions on bone or lymph node metastases. The dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18years
- Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
- Adenocarcinoma of the prostate treated with radical prostatectomy or radical RT
- Diagnosis of 1 to 3 metachronous metastases to bone or lymph nodes or oligoprogression / oligopersistance during ADT of a maximum of 3 metastases in bone or lymph nodes
- ECOG performance status of 0 - 1
Key exclusion criteria (7 listed)
- Visceral metastases
- Evidence of spinal cord compression (radiological or clinical)
- Concurrent malignancy
- Inability to undergo RT
- History of inflammatory colitis or other active severe comorbidities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RadiotherapyRT treatment Schedule as for clinical practice: Stereotactic body radiation treatment (SBRT) will be delivered with image guidance (image-guided radiation therapy or IGRT) and in the form of volumetric modulated arc therapy (VMAT). RT treatment Schedule: SBRT will be delivered in 1 to 6 fractions on bone or lymph node metastases. The dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints. | Procedure or surgery | Stereotactic body radiation treatment (SBRT) |
| androgen deprivation therapy (ADT)ADT as for clinical practice: * for oligorecurrent patients, ADT will be started at time of polimetastatic progression after SBRT; * for oligoprogressive patients, ADT will be continued during SBRT and untill polimetastatic progression | Drug | Stereotactic body radiation treatment (SBRT) |
| immune evaluationWe will use the flow cytometer FACSymphony, to analyse multiple immune populations from a limited sample of blood. We will monitor the dynamics of most innate (monocytic and granulocytic cells, Natural killer cells) and adaptive (T cells, B cells) immune subsets in the peripheral blood of PC patients before and after RT. We will deeply characterize CD4+ and CD8+ T cell subpopulations circulating in the patients enrolled in the study. In this attempt our panel will include markers of T cell differentiation and activation, including CD25, CD39, PD-1, CTL4, KLRG1, TIM3. We will analyse neutrophils subpopulations and investigate the functional profile of granulocytes in enrolled patients. Markers such as CD66b, CD24, CD16, MHC-II, LOX1, CD36 and CD62L will be included in our analysis. In conclusion our experimental strategy will result in a comprehensive profiling of the immune landscape in PC patients at single cell level. | Biological | Stereotactic body radiation treatment (SBRT) |
Primary outcome
immune evaluation
Time frame: from the baseline (before SBRT) to 7 days after the end of radiotherapy treatment
Analysis of the immunitary background performed before SBRT and evaluation of immune modulation after RT treatment. Our panels will include markers of T cell differentiation and activation, including CD25, CD39, PD-1, CTL4, KLRG1, TIM3, TIGIT. In addition we will investigate the phenotype and functional state of myeloid subsets in enrolled patients, comprising neutrophils, monocytes and dendritic cells. To this end, markers such as CD66b, CD24, CD16, MHC-II, LOX1, CD36 and CD62L will be included in our analysis.
2 secondary outcomes
Progression free survival
Time frame: 2 years
Prostate cancer specific survival (PCSS)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2025.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Radiotherapy, androgen deprivation therapy (ADT) and immune evaluation in people with Oligorecurrent and Oligoprogressive Prostate Cancer Patients, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
immune evaluation (time frame: from the baseline (before SBRT) to 7 days after the end of radiotherapy treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2025.