Clinical trial NCT05352178: Metastasis-directed Therapy for Oligorecurrent Prostate Cancer
Official title: a New Spark in Treating Oligorecurrent Prostate Cancer: Adding Systemic Treatment to Stereotactic Body Radiotherapy or Metastasectomy: Key to Long-lasting Event-free Survival?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Prostate Cancer Recurrent
Prostate Cancer Metastatic
Metastatic Cancer
Oligometastatic Disease
Oligometastasis
Hormone Sensitive Prostate Cancer
Keywords: Androgen deprivation therapy
Androgen receptor targeted agent
Stereotactic body radiation therapy
Metastasis-directed therapy
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2022-04-28
Enrollment: 873
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, three-arm, phase III trial
Primary purpose: TREATMENT

Brief summary: The aim is to investigate whether the addition of short-term androgen deprivation therapy (ADT) during 1 month or short-term ADT during 6 months together with an androgen receptor targeted therapy (ARTA) to metastasis-directed therapy (MDT) significantly prolongs poly-metastatic free survival (PMFS) and/or metastatic castration-refractory prostate cancer free survival (mCRPC-FS) in patients with oligorecurrent hormone sensitive prostate cancer.

Detailed description: Metastasis-directed therapy (MDT) has broadened the therapeutic window in patients presenting with oligorecurrent prostate cancer as it postpones the initiation of palliative androgen deprivation therapy (pADT) and its substantial side-effects for several years. Also from a biological point of view, this might be beneficial as the (early) use of ADT promotes the development of the lethal castrate-resistant state, whereby metastatic progression is driven by androgen-independent pathways. Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) or surgery has shown to be able to eradicate metastases with a significant advantage concerning the pADT-free survival compared to active surveillance. And the combination of SBRT with palliative systemic treatment significantly improved overall survival (OS) when compared tot systemic treatment alone.

One of the largest retrospective analyses (191 patients) on MDT for oligorecurrent prostate cancer has been conducted previously at UZ Leuven (doi: 10.3390/cancers12082271). Estimated median pADT-free survival was 66 months and estimated median mCRPC-free survival was not reached, but 83% of patients were still free of mCRPC at 10 years.

The addition of ADT to primary radiotherapy for intermediate of high risk prostate cancer or to salvage radiotherapy has shown to improve overall survival. Within the context of SBRT for oligorecurrent disease it is not yet known whether the addition of a certain period of ADT prolongs CRPC-free survival and if so, what should be the optimal duration of this ADT administration. Moreover, the addition of an androgen receptor targeted agent (ARTA) to ADT in men with metastatic hormone sensitive prostate cancer and a treated primary tumor resulted in significantly improved clinical outcomes, also in low-volume metastatic disease.

In this clinical trial the aim is to investigate whether the addition of short-term ADT during 1 month or short-term ADT during 6 months together with an ARTA to MDT significantly prolongs poly-metastatic free survival (PMFS) and/or metastatic castration-refractory prostate cancer free survival (mCRPC-FS) in patients with oligorecurrent hormone sensitive prostate cancer.

Eligibility criteria: Inclusion Criteria:

* Histologically proven initial diagnosis of prostate adenocarcinoma
* Priory treated and controlled primary tumor
* Biochemical recurrence defined by prostate-specific antigen (PSA) values \>0,2 ng/ml (i.e., two consecutive increases) following radical prostatectomy + postoperative radiotherapy and a PSA value of 2 ng/ml above the nadir after high-dose RT.
* Oligorecurrent disease defined as a maximum of 5 extracranial metastases in any organ, diagnosed on PSMA PET-CT or PSMA PET-MRI reported according to the E-PSMA consensus guidelines for interpretation of PSMA-PET (26). Nodal (N1) disease can be included only when accompanied by M1a-c disease, provided that the total number of spots does not exceed 5.
* Serum testosterone level within normal range.
* WHO performance 0-2
* Age \>= 18 years old
* Absence of psychological, sociological or geographical condition potentially hampering compliance with study protocol.
* Patients must be presented at the multidisciplinary board meeting and the inclusion in the trial needs approval by this board.
* Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
* 2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.

Exclusion Criteria:

* Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
* Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial
* Participation in an interventional Trial with an investigational medicinal product (IMP) or device
* Serum testosterone level at castration level.
* PSA rise while on active treatment (LHRH-agonist, LHRH antagonist, anti-androgen, maximal androgen blockade, oestrogen)
* Presence of poly-metastatic disease, defined as more than 5 metastatic lesions.
* Active malignancy other than prostate cancer that could potentially interfere with the interpretation of this trial.
* Previous treatments (RT, surgery) or comorbidities rendering new treatment with SBRT impossible.
* Contra indications for intake of enzalutamide (seizure or any condition that may predispose to seizure; significant cardiovascular disease within the last three months including myocardial infarction, unstable angina, congestive heart failure, ongoing arrythmias of grade \> 2 or a thromboembolic event).
* Not able to understand the treatment protocol or sign informed consent.

Primary outcomes:
measure: Poly-metastatic free survival (PMFS)
timeFrame: up to 5 years after MDT
Secondary outcomes:
measure: Metastatic castration-refractory prostate cancer free survival (mCRPC-FS)
timeFrame: up to 5 years after MDT
measure: Biochemical progression-free survival (bPFS)
timeFrame: up to 5 years after MDT
measure: Clinical progression free survival (cPFS)
timeFrame: up to 5 years after MDT
measure: Cancer Specific Survival (CSS)
timeFrame: up to 10 years after MDT
measure: Overall Survival (OS)
timeFrame: up to 10 years after MDT
measure: Acute and late toxicity scoring
timeFrame: up to 5 years after MDT
measure: Quality of life (QOL)
timeFrame: up to 5 years after MDT
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
Study officials:
References: