Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
400
Countries
1
Sites
28
low-volume metastatic castration-sensitive prostate cancer
To evaluate whether the discontinuation of ARSIs 12 months after its initiation in low-volume metastatic castration-sensitive prostate cancer (mCSPC) patients with the possibility to restart treatment, is non-inferior to continued androgen receptor signaling inhibitors (ARSI), thereby sparing significant toxicity and c…
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male
- Therapeutic area
- Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Neoplasms [C04]
- Trial duration
- 2 Feb 2024 → ongoing
- Decision date (initial)
- 2023-12-12
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Stichting Treatmeds
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
To evaluate whether the discontinuation of ARSIs 12 months after its initiation in low-volume metastatic castration-sensitive prostate cancer (mCSPC) patients with the possibility to restart treatment, is non-inferior to continued androgen receptor signaling inhibitors (ARSI), thereby sparing significant toxicity and costs
Secondary objectives 11
- To prospectively evaluate time to PSA increase
- To prospectively evaluate time to first line therapy for metastatic castration-resistant prostate cancer (mCRPC)
- to prospectively evaluate overall survival (OS)
- To correlate ctDNA levels to PSA levels, and to evaluate whether ctDNA levels could serve as a (better) treatment response marker than PSA
- To correlate PSMA-PET scan results to clinical outcomes
- To assess patients who will need continued ARSI treatment based on ctDNA levels before stopping treatment
- To correlate genomic profiles of previously taken prostate cancer biopsies to clinical outcomes
- To assess the value of ctDNA quantification during ARSIs treatment to predict tumor progression
- To explore QoL benefit by the interruption of ARSIs and potential changes during rechallenge
- To explore QoL with functional assessment of cancer therapy-prostate (FACT-P) at baseline, 12,18, 24 and 36 months after start treatmentTo identify resistance mechanisms in ctDNA occurring with ARSI treatment
- To explore whether intermittent dosing may prolong time to castration resistance prostate cancer plus ARSI resistance
Conditions and MedDRA coding
low-volume metastatic castration-sensitive prostate cancer
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Treatment phase From inclusion until last day of treatment with apalutamide or enzalutamide
|
Not Applicable | None | ||
| 2 | Randomization After 12 months in treatment phase, patients will be randomized to either continue or discontinue apalutamide or enzalutamide. In the first case patient stays in treatment phase, otherwise patient enters follow up phase
|
Randomised Controlled | None | Continue group: Patient who will continue treatment with ARSI after the first 12 months Discontinue group: Patients who will discontinue treatment with ARSI and will enter follow up phase |
|
| 3 | Follow up phase From last day of treatment or moment of progression (whichever occurs first) until death or end of study (whichever occurs first)
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Male and ≥18 years of age
- Histological diagnosis of prostate adenocarcinoma
- Low-volume de novo metastatic disease (M1a or M1b) defined as anything other than fitting the criteria for high-volume metastatic disease, e.g., four or more bone lesions with one or more lesions in any body structure beyond the spine or pelvis, or visceral disease (non-nodal). This has been assessed by either bone scan and computed tomography (CT), or PSMA-PET scan. Low-volume disease has subsequently been confirmed by the local (multidisciplinary) team after consideration of the available imaging results as per the standard imaging protocol for the site.
- ADT initiated within 6 weeks prior to inclusion
- Eastern Cooperative Oncology Group (ECOG) performance scale status of 0, 1 or 2
- Fit for treatment with apalutamide or enzalutamide according to treating physician
- Capable of understanding and complying with protocol requirements and able to understand and sign the informed consent form
Exclusion criteria 5
- Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
- Other prior malignancy less than or equal to 5 years prior to randomization except for squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer
- History of seizures or medications known to lower seizure threshold
- Any other prior treatment for prostate cancer other than ADT (e.g., other next generation anti-androgens or other CYP17 inhibitors, chemotherapy, immunotherapy, or radiopharmaceutical agents)
- ADT started more than 6 weeks before inclusion
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Time to clinical progression free survival (cPFS) in both arms
Secondary endpoints 9
- Overall survival (OS)
- Time to PSA increase (defined according to PCWG3 criteria)
- Time to first line therapy for mCRPC
- ctDNA levels correlation with PSA levels
- Value of ctDNA quantification during ARSI treatment to predict tumor progression
- Quality of life (QoL) in relation to treatment with ARSI
- To correlate PSMA-PET scan results to clinical outcomes
- Correlation of genomic profiles of previously taken prostate cancer tissue biopsies and clinical outcome.
- Predict patients who will need continued ARSI treatment with ctDNA levels
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SUB189031 · Substance
- Active substance
- Apalutamide
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 240 mg milligram(s)
- Max total dose
- 438000 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB77412 · Substance
- Active substance
- Enzalutamide
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 160 mg milligram(s)
- Max total dose
- 292000 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 16
Suprefact Depot 9,45 mg implantat
PRD7966367 · Product
- Pharmaceutical form
- IMPLANT
- Route of administration
- IMPLANTATION
- Max daily dose
- 9.9 mg milligram(s)
- Max total dose
- 198 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE01 — BUSERELIN
- Marketing authorisation
- 13372
- MA holder
- CHEPLAPHARM ARZNEIMITTEL GMBH
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Decapeptyl-CR 3,75 mg, poeder en oplosmiddel voor suspensie voor injectie
PRD468913 · Product
- Active substance
- Triptorelin
- Substance synonyms
- TRIPTORELINE
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- INJECTABLE SOLUTION
- Max daily dose
- 3.75 mg milligram(s)
- Max total dose
- 245 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE04 — TRIPTORELIN
- Marketing authorisation
- RVG 12450
- MA holder
- FERRING B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Pamorelin 22,5 mg, poeder en oplosmiddel voor suspensie voor injectie, met verlengde afgifte.
PRD391067 · Product
- Active substance
- Triptorelin
- Substance synonyms
- TRIPTORELINE
- Pharmaceutical form
- PROLONGED-RELEASE SUSPENSION FOR INJECTION
- Route of administration
- INTRAMUSCULAR INJECTION
- Max daily dose
- 22.5 mg milligram(s)
- Max total dose
- 225 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE04 — TRIPTORELIN
- Marketing authorisation
- RVG 103585
- MA holder
- IPSEN FARMACEUTICA B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Gonapeptyl Depot 3,75 mg poeder en oplosmiddel voor suspensie voor injectie
PRD435822 · Product
- Active substance
- Triptorelin
- Substance synonyms
- TRIPTORELINE
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 3.75 mg milligram(s)
- Max total dose
- 450 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE04 — TRIPTORELIN
- Marketing authorisation
- BE230027
- MA holder
- FERRING N.V.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Pamorelin 3,75 mg, poeder en oplosmiddel voor suspensie voor injectie, met verlengde afgifte.
PRD391051 · Product
- Active substance
- Triptorelin
- Substance synonyms
- TRIPTORELINE
- Pharmaceutical form
- PROLONGED-RELEASE SUSPENSION FOR INJECTION
- Route of administration
- INTRAMUSCULAR OR SUBCUTANEOUS
- Max daily dose
- 3.75 mg milligram(s)
- Max total dose
- 225 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE04 — TRIPTORELIN
- Marketing authorisation
- RVG 33849
- MA holder
- IPSEN FARMACEUTICA B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Pamorelin 11,25 mg, poeder en oplosmiddel voor suspensie voor injectie, met verlengde afgifte.
PRD391063 · Product
- Active substance
- Triptorelin
- Substance synonyms
- TRIPTORELINE
- Pharmaceutical form
- PROLONGED-RELEASE SUSPENSION FOR INJECTION
- Route of administration
- INTRAMUSCULAR INJECTION
- Max daily dose
- 11.25 mg milligram(s)
- Max total dose
- 225 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE04 — TRIPTORELIN
- Marketing authorisation
- RVG 31138
- MA holder
- IPSEN FARMACEUTICA B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
CAMCEVI 42 mg prolonged-release suspension for injection
PRD9731523 · Product
- Active substance
- Leuprorelin
- Substance synonyms
- LEUPROLIDE
- Pharmaceutical form
- PROLONGED-RELEASE SUSPENSION FOR INJECTION
- Route of administration
- IMPLANTATION
- Max daily dose
- 42 mg milligram(s)
- Max total dose
- 420 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE02 — LEUPRORELIN
- Marketing authorisation
- EU/1/22/1647/001
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02900MIG · Substance
- Active substance
- Leuprorelin Acetate
- Pharmaceutical form
- POWDER AND SOLVENT FOR SUSPENSION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 11.25 mg milligram(s)
- Max total dose
- 225 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02900MIG · Substance
- Active substance
- Leuprorelin Acetate
- Pharmaceutical form
- POWDER AND SOLVENT FOR SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 3.75 mg milligram(s)
- Max total dose
- 225 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Eligard 22,5 mg poeder en oplosmiddel voor oplossing voor injectie
PRD8990123 · Product
- Active substance
- Leuprorelin Acetate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 22.5 mg milligram(s)
- Max total dose
- 450 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE02 — LEUPRORELIN
- Marketing authorisation
- RVG 31669
- MA holder
- RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA S.P.A.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
ELIGARD 7.5 mg powder and solvent for solution for injection
PRD9148700 · Product
- Active substance
- Leuprorelin Acetate
- Substance synonyms
- LEUPROLIDE ACETATE
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 7.5 mg milligram(s)
- Max total dose
- 450 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE02 — LEUPRORELIN
- Marketing authorisation
- PA0812/005/001
- MA holder
- RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA S.P.A.
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02900MIG · Substance
- Active substance
- Leuprorelin Acetate
- Pharmaceutical form
- POWDER AND SOLVENT FOR SUSPENSION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Eligard 45 mg poeder en oplosmiddel voor oplossing voor injectie
PRD8990124 · Product
- Active substance
- Leuprorelin Acetate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 45 mg milligram(s)
- Max total dose
- 450 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE02 — LEUPRORELIN
- Marketing authorisation
- RVG 35313
- MA holder
- RECORDATI INDUSTRIA CHIMICA E FARMACEUTICA S.P.A.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Leuproreline Sandoz depot 3 maanden 5 mg, implantaat
PRD744667 · Product
- Active substance
- Leuprorelin
- Pharmaceutical form
- IMPLANT
- Route of administration
- IMPLANTATION
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 100 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02AE02 — LEUPRORELIN
- Marketing authorisation
- RVG 30594
- MA holder
- SANDOZ B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02400MIG · Substance
- Active substance
- Goserelin Acetate
- Pharmaceutical form
- IMPLANT
- Route of administration
- IMPLANTATION
- Max daily dose
- 10.8 mg milligram(s)
- Max total dose
- 234 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB02400MIG · Substance
- Active substance
- Goserelin Acetate
- Pharmaceutical form
- IMPLANT
- Route of administration
- IMPLANTATION
- Max daily dose
- 3.6 mg milligram(s)
- Max total dose
- 216 mg milligram(s)
- Max treatment duration
- 60 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Khrystany Isebia
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Khrystany Isebia
Locations
1 EU/EEA country · 28 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 400 | 28 |
| Rest of world | — | 0 | — |
Investigational sites
Deventer Ziekenhuis
Medical Oncology, Nico Bolkesteinlaan 75, 7416 SE, Deventer
Universiteit Maastricht
Medical Oncology, P Debyelaan 25, 6229 HX, Maastricht
Wilhelmina Ziekenhuis Assen
Medical Oncology, Europaweg-Zuid 1, 9401 RK, Assen
Ikazia Ziekenhuis
Internal Medicine, Montessoriweg 1, 3083 AN, Rotterdam
Laurentius Ziekenhuis Roermond
Medical oncology, Monseigneur Driessenstraat 6, 6043 CV, Roermond
Sint Antonius Ziekenhuis Stichting
Medical oncology, Koekoekslaan 1, 3435 CM, Nieuwegein
Ziekenhuisgroep Twente Stichting
Oncology, Zilvermeeuw 1, 7609 PP, Almelo
Bravis Ziekenhuis
Medical Oncology, Boerhaavelaan 25, 4708 AE, Roosendaal
Sint Franciscus Vlietland Groep Stichting
Medical Oncology, Kleiweg 500, 3045 PM, Rotterdam
Universitair Medisch Centrum Groningen
Medical Oncology, Hanzeplein 1, 9713 GZ, Groningen
Meander Medisch Centrum
Medical Oncology, Maatweg 3, 3813 TZ, Amersfoort
Adrz
Internal Medicine, 's-Gravenpolderseweg 114, 4462 RA, Goes
Medisch Spectrum Twente
Internal Medicine, Koningsplein 1, 7512 KZ, Enschede
Maasstad Ziekenhuis Stichting
Oncology, Maasstadweg 21, 3079 DZ, Rotterdam
Stichting Viecuri Medisch Centrum voor Noord-Limburg
General Medicine, Tegelseweg 210, 5912 BL, Venlo
Haaglanden Medisch Centrum Stichting
Internal Oncology, Lijnbaan 32, 2512 VA, 'S-Gravenhage
Tergooiziekenhuizen
Medical oncology, Laan Van Tergooi 2, 1212 VG, Hilversum
Noordwest Ziekenhuisgroep Stichting
Oncology, Wilhelminalaan 12, 1815 JD, Alkmaar
Spaarne Gasthuis Stichting
Medical oncology, Boerhaavelaan 24, 2035 RC, Haarlem
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Medical Oncology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Medisch Centrum Leeuwarden B.V.
Medical Oncology, Henri Dunantweg 2, 8934 AD, Leeuwarden
Canisius Wilhelmina Hospital
Urology, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Medical oncology, Plesmanlaan 121, 1066 CX, Amsterdam
Rode Kruis Ziekenhuis B.V.
Oncology, Vondellaan 13, 1942 LE, Beverwijk
Haga Hospital
Oncology, Els Borst-Eilersplein 275, 2545 AA, 's-Gravenhage
Stichting Treant Ziekenhuiszorg
Medical Oncology, Boermarkeweg 60, 7824 AA, Emmen
Amsterdam UMC
Medical Oncology, De Boelelaan 1117, 1081 HV, Amsterdam
Catharina Ziekenhuis Stichting
Medical Oncology, Michelangelolaan 2, 5623 EJ, Eindhoven
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-02-02 | 2024-10-17 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1 APA ENZA Short_Protocol_clean | 5 |
| Recruitment arrangements (for publication) | K1 Recruitment arrangements | 1 |
| Subject information and informed consent form - Extract (for publication) | Verklaring ApaEnza short_20052024_TvD 1 | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF adults 2023-506698-36_CLEAN | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 IMP_SmPC Apalutamide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2 IMP_SmPC Enzalutamide | 1 |
| Synopsis of the protocol (for publication) | D1 Protocol Synopsis_EN 2023-506698-36 | 4 |
| Synopsis of the protocol (for publication) | D1 Protocol Synopsis_NL 2023-506698-36 | 3 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-27 | Netherlands | Acceptable with conditions 2023-10-04
|
2023-12-12 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2023-12-13 | Netherlands | Acceptable with conditions 2023-10-04
|
2023-12-13 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-07-24 | Netherlands | Acceptable 2024-10-10
|
2024-10-10 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-07-21 | Netherlands | Acceptable 2025-10-13
|
2025-10-13 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-10-30 | Netherlands | Acceptable 2025-10-13
|
2025-10-30 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-12-03 | Netherlands | Acceptable 2025-10-13
|
2025-12-03 |