Prostate CancerPhase 2/3LOBSTERNCT04242017
Long-term Better Than Short-term ADT With Salvage RT
A Phase 2/3 study testing Triptoreline in people with Prostate Cancer, run by Universitaire Ziekenhuizen KU Leuven at 3 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Triptoreline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 394 participants
- Where
- 3 sitesBelgium
- Study dates
- 7 Jul 2020to 1 Feb 2031
- Phase
- Phase 2/3
- 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 Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium3 sites, 3 recruiting
- Recruiting
AZ Maria Middelares
Ghent
Filip Ameye
- Recruiting
UZ Gent
Ghent
Valérie Fonteyne
- Recruiting
UZ Leuven
Leuven
UZ Leuven, gert.demeerleer@uzleuven.be
About this study
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
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.
Read the 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
- Conditions
- Prostate Cancer
- Being tested
- Triptoreline
- Keywords
- pN0, biochemical recurrence, salvage radiation therapy, hormonal treatment
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriptorelineDrug
Comparison of the duration of ADT (Triptoreline)
| Study group | Role | What they receive |
|---|---|---|
| salvage RT + 6 months ADT | Active comparator | 70 Gy to the prostate bed (2 Gy/fraction) + 6 months ADT Receives: Drug: Triptoreline |
| salvage RT + 24 months ADT | Experimental | 70 Gy to the prostate bed (2 Gy/fraction) + 24 months ADT Receives: Drug: Triptoreline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metastasis-free survival
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.
Measured: 5 years
Secondary outcomes (11)
Pelvic recurrence-free survival
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.
Measured: up to 10 years after randomization
Clinical progression-free survival
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.
Measured: up to 10 years after randomization
(Palliative) Systemic therapy-free survival
time to the start of palliative ADT
Measured: up to 20 years (or more) after randomization
Time to CRPC
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.
Measured: up to 20 years (or more) after randomization
Cause-specific survival (CSS)
freedom from dying from prostate cancer (K-M statistics)
Measured: up to 20 years (or more) after randomization
Overall survival (OS)
freedom from dying from any cause (K-M statistics)
Measured: up to 20 years (or more) after randomization
Acute toxicity
adverse effects according to the CTCAE version 4.0
Measured: during RT, up to three months after radiation therapy
Late toxicity
adverse effects according to the CTCAE version 4.0
Measured: starting from more than three months after radiation therapy, up to 5 years after radiotherapy
Quality of life assessment
EORTC QLQ-C30
Measured: up to 5 years after randomization
Quality of life assessment
EORTC QLQ-PR25
Measured: up to 5 years after randomization
Quality of life assessment
EQ-5D-5L
Measured: up to 5 years after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2020
- Study start7 Jul 2020
- Primary completion1 Feb 2026 (estimated)
- Study completion1 Feb 2031 (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 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 394 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Ipsen
- Responsible party
- Sponsor
- Investigators
- Gert De Meerleer, MD, PhD, Study chair, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04242017
- Sponsor's protocol ID
- S61996
- Acronym
- LOBSTER
- Status last verified
- Dec 2023
- First submitted
- 21 Jan 2020
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32666822
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04242017
- Acronym / sponsor ID
- LOBSTER / S61996
- Conditions
- Prostate Cancer
- Keywords
- pN0, biochemical recurrence, salvage radiation therapy, hormonal treatment
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 394 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- Ipsen
- Study start
- 7 Jul 2020 (actual)
- Primary completion
- 1 Feb 2026 (estimated)
- Study completion
- 1 Feb 2031 (estimated)
- First posted
- 27 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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| salvage RT + 6 months ADT | Active comparator | Drug: Triptoreline70 Gy to the prostate bed (2 Gy/fraction) + 6 months ADT |
| salvage RT + 24 months ADT | Experimental | Drug: Triptoreline70 Gy to the prostate bed (2 Gy/fraction) + 24 months ADT |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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…)
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 |
|---|---|---|
| TriptorelineComparison of the duration of ADT (Triptoreline) | Drug | salvage RT + 24 months ADT, salvage RT + 6 months ADT |
Primary outcome
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.
11 secondary outcomes
Pelvic recurrence-free survival
Time frame: up to 10 years after randomization
Clinical progression-free survival
Time frame: up to 10 years after randomization
(Palliative) Systemic therapy-free survival
Time frame: up to 20 years (or more) after randomization
Time to CRPC
Time frame: up to 20 years (or more) after randomization
Cause-specific survival (CSS)
Time frame: up to 20 years (or more) after randomization
Overall survival (OS)
Time frame: up to 20 years (or more) after randomization
Acute toxicity
Time frame: during RT, up to three months after radiation therapy
Late toxicity
Time frame: starting from more than three months after radiation therapy, up to 5 years after radiotherapy
Quality of life assessment
Time frame: up to 5 years after randomization
Quality of life assessment
Time frame: up to 5 years after randomization
Quality of life assessment
Time frame: up to 5 years after randomization
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 13 Dec 2023.
- Derived from this study: PubMed 32666822Berghen 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.
- Individual participant dataSharing planned: No
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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.
Gert De Meerleer, MD, PhD study chair
UZ Leuven
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Triptoreline in people with Prostate Cancer, run by Universitaire Ziekenhuizen KU Leuven at 3 sites 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 6 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 13 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 3 sites 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Charlien Berghen, MD (003216345217 ext. 003216345217, charlien.berghen@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metastasis-free survival (time frame: 5 years). 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 NCT04242017, 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 13 Dec 2023.