Long-term Better Than Short-term ADT With Salvage RT (LOBSTER)
|ClinicalTrials.gov Identifier: NCT04242017|
Recruitment Status : Not yet recruiting
First Posted : January 27, 2020
Last Update Posted : January 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Triptoreline||Phase 2 Phase 3|
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||394 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||randomized controlled trial|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||February 1, 2020|
|Estimated Primary Completion Date :||February 1, 2024|
|Estimated Study Completion Date :||February 1, 2029|
Active Comparator: salvage RT + 6 months ADT
70 Gy to the prostate bed (2 Gy/fraction) + 6 months ADT
Comparison of the duration of ADT (Triptoreline)
Experimental: salvage RT + 24 months ADT
70 Gy to the prostate bed (2 Gy/fraction) + 24 months ADT
Comparison of the duration of ADT (Triptoreline)
- Metastasis-free survival [ Time Frame: 5 years ]Time to appearance of M1a-b-c disease. In order to assess the absence/presence of M1a-M1c disease as early as possible, top-of-the-line imaging will be conducted in case of BR during follow-up after SRT and after agreement of the multidisciplinary uro-oncology team. Time point zero is the last day of radiotherapy (also applies for secondary endpoints). Top of the line imaging includes: CT thorax abdomen and bone scintigraphy (standard). PSMA PET-CT is allowed but not obligatory. Patients who are also included in the diagnostic imaging study are required to receive a PSMA PET-CT. Whole body MRI is allowed but not obligatory. BR is defined as any rise in PSA above the level of 0.2 ng/ml after a postradiotherapy nadir or a continued rise in the serum PSA despite salvage treatment (3). In case a BR is not accompanied by metastatic progression, PSMA PET/CT will be repeated every 6 months or earlier in case of prostate cancer-related symptoms.
- Pelvic recurrence-free survival [ Time Frame: up to 10 years after randomization ]time to appearance of local recurrence (prostate bed) and/or N1 disease (positive lymph node(s) below the aortic bifurcation) using PSMA PET/CT and triggered by biochemical relapse.
- Clinical progression-free survival [ Time Frame: up to 10 years after randomization ]time to appearance of any recurrence (local recurrence, N1 (positive lymph node(s) below the aortic bifurcation), M1a-c disease) and triggered by biochemical relapse.
- (Palliative) Systemic therapy-free survival [ Time Frame: up to 20 years (or more) after randomization ]time to the start of palliative ADT
- Time to CRPC [ Time Frame: up to 20 years (or more) after randomization ]time to biochemical and/or clinical progression at castrate testosterone levels (<50 ng/dl). Progression is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of > 2 ng/ml and a rise of 50% of the nadir PSA level, progression of bone lesions (2 or more new bone lesions detected on bone scan), progression of soft tissue lesions according to RECIST criteria or the appearance of one or more new visceral or soft tissue (inclusive lymph node) metastasis.
- Cause-specific survival (CSS) [ Time Frame: up to 20 years (or more) after randomization ]freedom from dying from prostate cancer (K-M statistics)
- Overall survival (OS) [ Time Frame: up to 20 years (or more) after randomization ]freedom from dying from any cause (K-M statistics)
- Acute toxicity [ Time Frame: during RT, up to three months after radiation therapy ]adverse effects according to the CTCAE version 4.0
- Late toxicity [ Time Frame: starting from more than three months after radiation therapy, up to 5 years after radiotherapy ]adverse effects according to the CTCAE version 4.0
- Quality of life assessment [ Time Frame: up to 5 years after randomization ]EORTC QLQ-C30
- Quality of life assessment [ Time Frame: up to 5 years after randomization ]EORTC QLQ-PR25
- Quality of life assessment [ Time Frame: up to 5 years after randomization ]EQ-5D-5L
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04242017
|Contact: Charlien Berghen, MD||003216345217 ext email@example.com|
|Contact: Gert De Meerleer, MD, PhD||003216347600 ext firstname.lastname@example.org|
|Study Chair:||Gert De Meerleer, MD, PhD||UZ Leuven|