Metastasis-directed Therapy in Castration-refractory Prostate Cancer (MEDCARE)
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|ClinicalTrials.gov Identifier: NCT04222634|
Recruitment Status : Recruiting
First Posted : January 10, 2020
Last Update Posted : January 18, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Castration-resistant Prostate Cancer||Other: Radiotherapy (SBRT) and/or surgery (metastasectomy)||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||single arm study|
|Masking:||None (Open Label)|
|Official Title:||Metastasis-directed Therapy in Castration-refractory Prostate Cancer MEDCARE : a Non-randomized Phase 2 Trial|
|Actual Study Start Date :||December 27, 2019|
|Estimated Primary Completion Date :||January 1, 2023|
|Estimated Study Completion Date :||January 1, 2030|
MDT for oligoprogressive lesions in CRPC
Other: Radiotherapy (SBRT) and/or surgery (metastasectomy)
Metastasis-directed therapy (surgery and/or radiotherapy) as treatment for oligoprogressive lesions
- 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.
- PSA response [ Time Frame: up to 5 years after MDT ]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.
- Clinical progression-free survival (cPFS) [ Time Frame: up to 5 years after MDT ]Progression is defined as the appearance of any recurrence (local, nodal or metastatic) on conventional imaging.
- Cancer-specific survival (CSS) [ Time Frame: up to 10 years after MDT ]CSS is calculated from last day of treatment until PCa death
- Overall survival (OS) [ Time Frame: up to 10 years after MDT ]Overall survival (OS) will be calculated from last day of treatment until death from any cause.
- Acute and late toxicity (in case of radiotherapy) [ Time Frame: up to 5 years after MDT ]Acute and late toxicity as a result of radiotherapy will be scored using the Common Toxicity Criteria Version 5.0 (24).
- Surgical complications (in case of surgery) [ Time Frame: up to 5 years after MDT ]Surgical complications will be scored using Clavien-Dindo Classification (25) Toxicity will be scored at every follow-up visit.
- Quality-of-life (QOL) [ Time Frame: up to 5 years after MDT ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04222634
|Contact: Charlien Berghenfirstname.lastname@example.org|
|Contact: Gert De Meerleeremail@example.com|
|Gert De Meerleer||Recruiting|
|Leuven, Belgium, 3000|
|Contact: Gert De Meerleer 003216347600 ext 003216347600 firstname.lastname@example.org|
|Principal Investigator:||Gert De Meerleer, Ph.D., M.D.||UZ Leuven|