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Long-term Better Than Short-term ADT With Salvage RT (LOBSTER)

Primary Purpose

Prostate Cancer

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Triptoreline

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring pN0, biochemical recurrence, salvage radiation therapy, hormonal treatment

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

salvage RT + 6 months ADT

salvage RT + 24 months ADT

Arm Description

70 Gy to the prostate bed (2 Gy/fraction) + 6 months ADT

70 Gy to the prostate bed (2 Gy/fraction) + 24 months ADT

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

(Palliative) Systemic therapy-free survival

time to the start of palliative ADT

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.

Cause-specific survival (CSS)

freedom from dying from prostate cancer (K-M statistics)

Overall survival (OS)

freedom from dying from any cause (K-M statistics)

Acute toxicity

adverse effects according to the CTCAE version 4.0

Late toxicity

adverse effects according to the CTCAE version 4.0

Quality of life assessment

EORTC QLQ-C30

Quality of life assessment

EORTC QLQ-PR25

Quality of life assessment

EQ-5D-5L

Full Information

NCT ID

NCT04242017

First Posted

January 21, 2020

Last Updated

January 24, 2020

Sponsor

Universitaire Ziekenhuizen KU Leuven

Collaborators

Ipsen

1. Study Identification

Unique Protocol Identification Number

NCT04242017

Brief Title

Long-term Better Than Short-term ADT With Salvage RT

Acronym

LOBSTER

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

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Not yet recruiting

Study Start Date

February 1, 2020 (Anticipated)

Primary Completion Date

February 1, 2024 (Anticipated)

Study Completion Date

February 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Universitaire Ziekenhuizen KU Leuven

Collaborators

Ipsen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

pN0, biochemical recurrence, salvage radiation therapy, hormonal treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

randomized controlled trial

Masking

None (Open Label)

Allocation

Randomized

Enrollment

394 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

salvage RT + 6 months ADT

Arm Type

Active Comparator

Arm Description

70 Gy to the prostate bed (2 Gy/fraction) + 6 months ADT

Arm Title

salvage RT + 24 months ADT

Arm Type

Experimental

Arm Description

70 Gy to the prostate bed (2 Gy/fraction) + 24 months ADT

Intervention Type

Drug

Intervention Name(s)

Triptoreline

Intervention Description

Comparison of the duration of ADT (Triptoreline)

Primary Outcome Measure Information:

Title

Metastasis-free survival

Description

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Pelvic recurrence-free survival

Description

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.

Time Frame

up to 10 years after randomization

Title

Clinical progression-free survival

Description

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.

Time Frame

up to 10 years after randomization

Title

(Palliative) Systemic therapy-free survival

Description

time to the start of palliative ADT

Time Frame

up to 20 years (or more) after randomization

Title

Time to CRPC

Description

Time Frame

up to 20 years (or more) after randomization

Title

Cause-specific survival (CSS)

Description

freedom from dying from prostate cancer (K-M statistics)

Time Frame

up to 20 years (or more) after randomization

Title

Overall survival (OS)

Description

freedom from dying from any cause (K-M statistics)

Time Frame

up to 20 years (or more) after randomization

Title

Acute toxicity

Description

adverse effects according to the CTCAE version 4.0

Time Frame

during RT, up to three months after radiation therapy

Title

Late toxicity

Description

adverse effects according to the CTCAE version 4.0

Time Frame

starting from more than three months after radiation therapy, up to 5 years after radiotherapy

Title

Quality of life assessment

Description

EORTC QLQ-C30

Time Frame

up to 5 years after randomization

Title

Quality of life assessment

Description

EORTC QLQ-PR25

Time Frame

up to 5 years after randomization

Title

Quality of life assessment

Description

EQ-5D-5L

Time Frame

up to 5 years after randomization

10. Eligibility

Sex

Male

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Charlien Berghen, MD

Phone

003216345217

Ext

003216345217

charlien.berghen@uzleuven.be

First Name & Middle Initial & Last Name or Official Title & Degree

Gert De Meerleer, MD, PhD

Phone

003216347600

Ext

003216347600

gert.demeerleer@uzleuven.be

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gert De Meerleer, MD, PhD

Organizational Affiliation

UZ Leuven

Official's Role

Study Chair

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32666822

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.

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Long-term Better Than Short-term ADT With Salvage RT

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