Clinical trial NCT04242017: Long-term Better Than Short-term ADT With Salvage RT
Official title: A Randomized, Multicenter, Prospective Phase II Trial to Assess the Effect of Short- Versus Long-term Adjuvant ADT With High Dose Salvage Radiotherapy on Distant Metastasis Free Survival in Patients With Biochemical Relapse After Radical Prostatectomy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Prostate Cancer
Keywords: pN0
biochemical recurrence
salvage radiation therapy
hormonal treatment
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Ipsen
First posted: 2020-01-27
Enrollment: 394
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled trial
Primary purpose: TREATMENT

Brief summary: A randomized, multicenter, prospective PHASE II trial to assess the effect of short- versus long-term adjuvant ADT with high dose salvage radiotherapy on distant metastasis free survival in case of biochemical relapse (BR) after radical prostatectomy.

Detailed description: Radical prostatectomy (RP) is one of the standard treatment options for localized and locally advanced prostate cancer. RP should be combined with an extended pelvic lymph node dissection (ePLND) when the risk of pelvic involvement becomes substantial, at least 7%. In case of node-negative disease (pN0), adverse pathological features at examination of the RP-specimen such as extra-capsular extension (ECE), seminal vesicle invasion (SVI) and positive surgical margins (PSM) increase the risk of biochemical relapse (BR) and/or isolated local relapse (LR). Both a BR and LR, if not adequately treated, can finally result in the development of distant metastasis.

In case of BR and/or LR, salvage radiotherapy (SRT) is the only treatment option with curative intent. Several factors play a significant role in predicting the outcome after SRT: Gleason score, pre-SRT PSA, pre-SRT doubling time, SVI, SRT dose and duration of adjuvant androgen deprivation therapy (ADT) associated with SRT. The 2 latter variables have never been tested in a randomized controlled trial. The GETUG-AFU 16 trial randomized between no vs. 6 months ADT while patients received 66 Gy to the prostate bed and 46 Gy to the pelvis. Moreover, the pN0 status was not needed for inclusion. Also the RADICALS trial is currently running this comparison with a radiation dose of 66 Gy to the prostate bed and also no information on pN status is needed to be included in this study. In the LOBSTER study, the pN0 status is obligatory and the prescription dose is set at 70 Gy to the prostate bed and seminal vesicles. These conditions make this study unique compared to other already conducted and currently running trials.

In previous work, it has been demonstrated that ADT, added for 6 months to SRT, significantly improved biochemical relapse free survival at 5 years. Added to this, there is recent evidence that using a longer schedule of adjuvant ADT might be beneficial when compared to a 6-months schedule. Unfortunately, none of these suggestions are based on evidence coming from a randomized controlled trial.

Therefore, this randomized phase 2 trial 'LOBSTER' is conducted, comparing 6 versus 24 months of adjuvant ADT together with high-dose SRT in case of BR after RP in pN0 prostate cancer patients

Eligibility criteria: Inclusion Criteria:

* History of histologically proven prostate cancer, treated with RP and ePLND. All patients have to be pN0. The minimal template for ePLND is defined as the removal of the external iliac, internal iliac and obturator nodes (standard template). Removal of the presacral and common iliac nodes is left at the discretion of the treating urologist.
* Asymptomatic PSA-rise post-RP, defined as a value equal to or more than 0.2µg/l and at least confirmed once (interval ≥2 weeks, confirmation PSA level should be higher). In case of Gleason 8-10, pT3b or R1 resection, an asymptomatic PSA-rise post-RP starting from ≥0.15 µg/l is allowed for inclusion. If the PSA-level is less than 0.4 ng/ml, no additional staging for distant metastasis is required before inclusion in the trial. The patient will be offered the opportunity to participate in a diagnostic sub-study with investigational imaging with 18F PSMA PET CT. However in case of PSA-level \>0.4 ng/ml, biological imaging using 18F-PSMA or 68Ga-PSMA is mandatory as this is not considered investigational anymore. Therefore the patient cannot anymore take part in the diagnostic sub-study and (un-blinded) PET-CT is obligatory to rule out lymph node (N) and /or distant metastasis (M1a-c) before inclusion.
* Testosterone levels within above 150 ng/dl.
* ECOG 0-1
* Life expectancy more than 5 years
* Signed informed consent

Exclusion Criteria:

* Presence of pN1 disease at original surgical specimen.
* Presence of distant metastasis at time of referral (M1a-c). If PSA more than 0.4 ng/ml, imaging with PET-CT is required to rule out distant metastasis (see above). Other additional imaging modalities (CT scan, bone scintigraphy...) are allowed but left at the discretion of the treating centre.
* Undetectable PSA (less than 0.2 ng/ml) at time of referral.
* Previous RT making new RT impossible (overlapping treatment fields).
* Known contraindications to irradiation (Ulcerative Colitis, Crohn Disease, Ataxia Teleangiectasia...)
* Active treatment with ADT or PSA modulating drugs (finasteride, dutasteride, high-dose corticoids...)
* Not able understanding treatment protocol or signing informed consent.

Primary outcomes:
measure: Metastasis-free survival
timeFrame: 5 years
Secondary outcomes:
measure: Pelvic recurrence-free survival
timeFrame: up to 10 years after randomization
measure: Clinical progression-free survival
timeFrame: up to 10 years after randomization
measure: (Palliative) Systemic therapy-free survival
timeFrame: up to 20 years (or more) after randomization
measure: Time to CRPC
timeFrame: up to 20 years (or more) after randomization
measure: Cause-specific survival (CSS)
timeFrame: up to 20 years (or more) after randomization
measure: Overall survival (OS)
timeFrame: up to 20 years (or more) after randomization
measure: Acute toxicity
timeFrame: during RT, up to three months after radiation therapy
measure: Late toxicity
timeFrame: starting from more than three months after radiation therapy, up to 5 years after radiotherapy
measure: Quality of life assessment
timeFrame: up to 5 years after randomization
measure: Quality of life assessment
timeFrame: up to 5 years after randomization
measure: Quality of life assessment
timeFrame: up to 5 years after randomization
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: UZ Leuven
name: Gert De Meerleer, MD, PhD
role: STUDY_CHAIR
References:
citation: Berghen C, Joniau S, Laenen A, Devos G, Rans K, Goffin K, Haustermans K, Meerleer G. Long- versus short-term androgen deprivation therapy with high-dose radiotherapy for biochemical failure after radical prostatectomy: a randomized controlled trial. Future Oncol. 2020 Sep;16(27):2035-2044. doi: 10.2217/fon-2020-0390. Epub 2020 Jul 15.