Castration-resistant Prostate CancerMEDCARENCT04222634
Metastasis-directed Therapy in Castration-refractory Prostate Cancer
A study testing Radiotherapy (SBRT) and/or surgery (metastasectomy) in people with Castration-resistant Prostate Cancer, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
The aim is to define the postponement of next line systemic treatment (NEST), by the use of metastasis-directed therapy in patients with oligoprogressive castration-refractory prostate cancer. This will be defined by the NEST-free survival. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Castration-resistant Prostate Cancer
- What is being tested?
- Radiotherapy (SBRT) and/or surgery (metastasectomy)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteBelgium
- Study dates
- 27 Dec 2019to 1 Jan 2030
- 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
- Histologically proven initial diagnosis of adenocarcinoma of the prostate
- mCRPC setting, with testosterone level < 50 ng/dl or 1.7 nmol/l
- Oligoprogressive disease, defined as a maximum of 3 extracranial metastases in any organ system OR local recurrence, diagnosed on conventional imaging with CT and bone scan. This may present as either the progression of pre-existing disease, and/or the appearance of new metastases. (defined according to the PCWG 3 criteria (20), see section 6. Trial Procedures)
- Patients currently treated with ADT, whether or not combined with another systemic treatment such as abiraterone acetate, enzalutamide, docetaxel and radium-223. Denosumab is allowed but not considered as second-line systemic treatment.
- Priory treated primary tumor by radiotherapy or surgery. If the primary tumour is not treated, local therapy should be added to the treatment. Both radiotherapy as well as surgery are allowed.
- WHO performance status 0-1
Show all 10Show fewer
- Age >= 18 years old
- Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and/or follow-up schedule. Those conditions should be discussed with the patient before registration in the trial.
- Patient presented at the multidisciplinary tumour board of the local hospital.
- Before patient registration/randomization, written informed consent must be given according to ICH/GCO and national/local regulations.
Who cannot join
- Serum testosterone level > 50 ng/ml or > 1.7 nmol/l.
- Presence of polyprogression, defined as more than 3 progressive/new metastatic lesions and/or local recurrence (which counts for 1 lesion).
- Active malignancy other than prostate cancer that can potentially interfere with the interpretation of the trial.
- Previous treatments (RT, surgery) or comorbidities rendering PDT impossible.
- Disorder precluding understanding of trial information or informed consent or signing informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metastasis-directed Therapy in Castration-refractory Prostate Cancer MEDCARE : a Non-randomized Phase 2 Trial
The aim is to define the postponement of next line systemic treatment (NEST), by the use of metastasis-directed therapy in patients with oligoprogressive castration-refractory prostate cancer. This will be defined by the NEST-free survival.
Furthermore the investigators will use 18F PSMA PET-CT as investigational imaging, to assess the predictive value and impact on treatment policy.
Read the detailed description
When treatment with pADT is initiated in case of mHSPC, the sensitivity to castration will eventually disappear due to the out-selection of castration-refractory clones. At that moment, the stage of mCRPC is attained. In the setting of mCRPC, clinical and iconographic progression (and to a lesser extent biochemical progression) traditionally implies a switch to a next-line systemic treatment (NEST). However, within the group of these progressive patients, there is a subgroup showing oligoprogressive disease, which is defined as the progression of a limited number of metastatic spots, whereas the majority of metastases is controlled by the systemic therapy the patient is receiving at that time. This heterogeneous response to treatment reflects the heterogeneity of the clonogenic cells that give rise to mCRPC. The hypothesis of this trial is that treatment with MDT of these oligoprogressive lesions allow patients to remain on their current systemic therapy, thereby delaying the need for NEST.
A multicentric retrospective chart analysis on MDT for oligoprogressive CRPC has been conductedat previously the UZ Leuven together with UZ Gent (doi: 10.1016/j.euo.2019.08.012.). A total of 30 patients with oligoprogressive CRPC were selected for further analysis. In this population, after a median follow-up of 17 months (IQR 9;25), the median NEST-FS in the MDT group was 16 months (95% CI: 10-22 months). The median progression free survival (PFS) was 10 months (95% CI: 6-15 months). Subsequently, the investigators selected within the MDT group those cases who received SBRT or surgery (metastasectomy), as these patients will be the subjects in this phase 2 trial. There was a median NEST-free survival of 21 months (CI 95% 12-21 months) and a median PFS of 10 months (95% CI: 6-14 months). SBRT or surgery-related toxicity was minor, with limited grade 1 and 2 toxicity and only one patient experiencing late grade 3 GU/GI toxicity after treatment for local relapse in the prostate.
These findings of this retrospective analysis clearly show the need for further prospective investigation. Therefore, this prospective phase 2 trial was initiated in patients with oligoprogressive mCRPC who will receive MDT. If the primary tumor has not been treated yet, local treatment will be added. Ongoing systemic treatment will be continued until progression. The trial is explorative and still hypothesis generating. The results from this trial will serve as a guidance for a randomized phase 3 trial in the near future.
- Conditions
- Castration-resistant Prostate Cancer
- Being tested
- Radiotherapy (SBRT) and/or surgery (metastasectomy)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiotherapy (SBRT) and/or surgery (metastasectomy)Other
Metastasis-directed therapy (surgery and/or radiotherapy) as treatment for oligoprogressive lesions
| Study group | Role | What they receive |
|---|---|---|
| MDT for oligoprogressive lesions in CRPC | Other | metastasis-directed therapy:
* radiotherapy (SBRT or conventional radiotherapy in case of local recurrence or untreated primary tumor)
* metastasectomy
* salvage lymphadenectomy
* salvage prostatectomy in case of local recurrence or untreated primary tumor Receives: Other: Radiotherapy (SBRT) and/or surgery (metastasectomy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Next-line Systemic Treatment - free survival (NEST-FS)
Time until the start with a subsequent systemic treatment line calculated from the last day of MDT until the first day of NEST or death (whichever comes first)
Measured: up to 5 years after MDT
PSMA PET-CT accuracy and predictive value
We will evaluate if (1) at time of PSA progression, new lesions will be visible on PSMA PET-CT and not on conventional imaging or visible on both, (2) if those new lesions at time of radiographic progression were already visible as active lesions on PSMA PET-CT (and not on conventional imaging) at time of inclusion, and (3) we will evaluate if active lesions visible at PSMA PET-CT at initial diagnosis of oligoprogression/at time of inclusion, who are not visible on conventional imaging might disappear without targetet treatment. We will evaluate if PSMA PET-CT would result in a change of patient management.
Measured: up to 5 years after MDT
Secondary outcomes (7)
PSA response
A decline in PSA value ≥ 50% from baseline confirmed by a second value ≥ 4 weeks. Individual PSA change responses as a percentage change from baseline to week 12 will be plotted in a waterfall plot.
Measured: up to 5 years after MDT
Clinical progression-free survival (cPFS)
Progression is defined as the appearance of any recurrence (local, nodal or metastatic) on conventional imaging.
Measured: up to 5 years after MDT
Cancer-specific survival (CSS)
CSS is calculated from last day of treatment until PCa death
Measured: up to 10 years after MDT
Overall survival (OS)
Overall survival (OS) will be calculated from last day of treatment until death from any cause.
Measured: up to 10 years after MDT
Acute and late toxicity (in case of radiotherapy)
Acute and late toxicity as a result of radiotherapy will be scored using the Common Toxicity Criteria Version 5.0 (24).
Measured: up to 5 years after MDT
Surgical complications (in case of surgery)
Surgical complications will be scored using Clavien-Dindo Classification (25) Toxicity will be scored at every follow-up visit.
Measured: up to 5 years after MDT
Quality-of-life (QOL)
Quality of life scoring using the EORTC QLQ-30 supplemented with QLQ-PR25. We will assess the quality-of-life-years with the EuroQOL classification system (EQ-5D). Assessments are planned at baseline, last day of treatment, and during every follow-up consultation.
Measured: up to 5 years after MDT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2020
- Study start27 Dec 2019
- Primary completion25 Jul 2023
- Study completion1 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single arm study
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gert De Meerleer, Ph.D., M.D., Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04222634
- Sponsor's protocol ID
- S63177
- Acronym
- MEDCARE
- Status last verified
- Dec 2023
- First submitted
- 18 Dec 2019
- Last updated
- 7 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Participant data will be coded and available for the involved researcher and PI only (dr. Charlien Berghen and prof. dr. De Meerleer Gert)
Publications
Berghen C, Joniau S, Rans K, Devos G, Poels K, Slabbaert K, Dumez H, Albersen M, Goffin K, Haustermans K, De Meerleer G. Metastasis-directed therapy in castration-refractory prostate cancer (MEDCARE): a non-randomized phase 2 trial. BMC Cancer. 2020 May 24;20(1):457. doi: 10.1186/s12885-020-06853-x.
PubMed 32448171
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metastasis-directed Therapy in Castration-refractory Prostate Cancer MEDCARE : a Non-randomized Phase 2 Trial
- ClinicalTrials.gov ID
- NCT04222634
- Acronym / sponsor ID
- MEDCARE / S63177
- Conditions
- Castration-resistant Prostate Cancer
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 27 Dec 2019 (actual)
- Primary completion
- 25 Jul 2023 (actual)
- Study completion
- 1 Jan 2030 (estimated)
- First posted
- 10 Jan 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.
The aim is to define the postponement of next line systemic treatment (NEST), by the use of metastasis-directed therapy in patients with oligoprogressive castration-refractory prostate cancer. This will be defined by the NEST-free survival.
Furthermore the investigators will use 18F PSMA PET-CT as investigational imaging, to assess the predictive value and impact on treatment policy.
Detailed description
When treatment with pADT is initiated in case of mHSPC, the sensitivity to castration will eventually disappear due to the out-selection of castration-refractory clones. At that moment, the stage of mCRPC is attained. In the setting of mCRPC, clinical and iconographic progression (and to a lesser extent biochemical progression) traditionally implies a switch to a next-line systemic treatment (NEST). However, within the group of these progressive patients, there is a subgroup showing oligoprogressive disease, which is defined as the progression of a limited number of metastatic spots, whereas the majority of metastases is controlled by the systemic therapy the patient is receiving at that time. This heterogeneous response to treatment reflects the heterogeneity of the clonogenic cells that give rise to mCRPC. The hypothesis of this trial is that treatment with MDT of these oligoprogressive lesions allow patients to remain on their current systemic therapy, thereby delaying the need for NEST.
A multicentric retrospective chart analysis on MDT for oligoprogressive CRPC has been conductedat previously the UZ Leuven together with UZ Gent (doi: 10.1016/j.euo.2019.08.012.). A total of 30 patients with oligoprogressive CRPC were selected for further analysis. In this population, after a median follow-up of 17 months (IQR 9;25), the median NEST-FS in the MDT group was 16 months (95% CI: 10-22 months). The median progression free survival (PFS) was 10 months (95% CI: 6-15 months). Subsequently, the investigators selected within the MDT group those cases who received SBRT or surgery (metastasectomy), as these patients will be the subjects in this phase 2 trial. There was a median NEST-free survival of 21 months (CI 95% 12-21 months) and a median PFS of 10 months (95% CI: 6-14 months). SBRT or surgery-related toxicity was minor, with limited grade 1 and 2 toxicity and only one patient experiencing late grade 3 GU/GI toxicity after treatment for local relapse in the prostate.
These findings of this retrospective analysis clearly show the need for further prospective investigation. Therefore, this prospective phase 2 trial was initiated in patients with oligoprogressive mCRPC who will receive MDT. If the primary tumor has not been treated yet, local treatment will be added. Ongoing systemic treatment will be continued until progression. The trial is explorative and still hypothesis generating. The results from this trial will serve as a guidance for a randomized phase 3 trial in the near future.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single arm study
| Arm | Type | Receives |
|---|---|---|
| MDT for oligoprogressive lesions in CRPC | Other | Other: Radiotherapy (SBRT) and/or surgery (metastasectomy)metastasis-directed therapy: * radiotherapy (SBRT or conventional radiotherapy in case of local recurrence or untreated primary tumor) * metastasectomy * salvage lymphadenectomy * salvage prostatectomy in case of local recurrence or untreated primary tumor |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically proven initial diagnosis of adenocarcinoma of the prostate
- mCRPC setting, with testosterone level < 50 ng/dl or 1.7 nmol/l
- Oligoprogressive disease, defined as a maximum of 3 extracranial metastases in any organ system OR local recurrence, diagnosed on conventional imaging with CT and bone scan. This may present as either the progression of pre-existing disease, and/or the appearance of new metastases. (defined according to the PCWG 3 criteria (20), see section 6. Trial Procedures)
- Patients currently treated with ADT, whether or not combined with another systemic treatment such as abiraterone acetate, enzalutamide, docetaxel and radium-223. Denosumab is allowed but not considered as second-line systemic treatment.
- Priory treated primary tumor by radiotherapy or surgery. If the primary tumour is not treated, local therapy should be added to the treatment. Both radiotherapy as well as surgery are allowed.
Key exclusion criteria (5 listed)
- Serum testosterone level > 50 ng/ml or > 1.7 nmol/l.
- Presence of polyprogression, defined as more than 3 progressive/new metastatic lesions and/or local recurrence (which counts for 1 lesion).
- Active malignancy other than prostate cancer that can potentially interfere with the interpretation of the trial.
- Previous treatments (RT, surgery) or comorbidities rendering PDT impossible.
- Disorder precluding understanding of trial information or informed consent or signing informed consent.
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 |
|---|---|---|
| Radiotherapy (SBRT) and/or surgery (metastasectomy)Metastasis-directed therapy (surgery and/or radiotherapy) as treatment for oligoprogressive lesions | Other | MDT for oligoprogressive lesions in CRPC |
Primary outcome
Next-line Systemic Treatment - free survival (NEST-FS)
Time frame: up to 5 years after MDT
Time until the start with a subsequent systemic treatment line calculated from the last day of MDT until the first day of NEST or death (whichever comes first)
PSMA PET-CT accuracy and predictive value
Time frame: up to 5 years after MDT
We will evaluate if (1) at time of PSA progression, new lesions will be visible on PSMA PET-CT and not on conventional imaging or visible on both, (2) if those new lesions at time of radiographic progression were already visible as active lesions on PSMA PET-CT (and not on conventional imaging) at time of inclusion, and (3) we will evaluate if active lesions visible at PSMA PET-CT at initial diagnosis of oligoprogression/at time of inclusion, who are not visible on conventional imaging might disappear without targetet treatment. We will evaluate if PSMA PET-CT would result in a change of patient management.
7 secondary outcomes
PSA response
Time frame: up to 5 years after MDT
Clinical progression-free survival (cPFS)
Time frame: up to 5 years after MDT
Cancer-specific survival (CSS)
Time frame: up to 10 years after MDT
Overall survival (OS)
Time frame: up to 10 years after MDT
Acute and late toxicity (in case of radiotherapy)
Time frame: up to 5 years after MDT
Surgical complications (in case of surgery)
Time frame: up to 5 years after MDT
Quality-of-life (QOL)
Time frame: up to 5 years after MDT
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 7 Dec 2023.
- Derived from this study: PubMed 32448171Berghen C, Joniau S, Rans K, Devos G, Poels K, Slabbaert K, Dumez H, Albersen M, Goffin K, Haustermans K, De Meerleer G. Metastasis-directed therapy in castration-refractory prostate cancer (MEDCARE): a non-randomized phase 2 trial. BMC Cancer. 2020 May 24;20(1):457. doi: 10.1186/s12885-020-06853-x.
- Individual participant dataSharing planned: No. Participant data will be coded and available for the involved researcher and PI only (dr. Charlien Berghen and prof. dr. De Meerleer Gert)
Related trials for Castration-resistant Prostate Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
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.
Gert De Meerleer, Ph.D., M.D. principal investigator
UZ Leuven
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 (SBRT) and/or surgery (metastasectomy) in people with Castration-resistant Prostate Cancer, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 10 inclusion and 5 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 7 Dec 2023. 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 Belgium. 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?
Next-line Systemic Treatment - free survival (NEST-FS) (time frame: up to 5 years after MDT). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04222634, which also lists 1 linked publication.
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 7 Dec 2023.