E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
men with biochemical recurrent prostate cancer after radical prostatectomy with ≤ 4 foci harbouring regional lymph node metastases (up to 6 lymph nodes in total) on nano-MRI. |
patiënten met biochemisch recidief prostaatcarcinoom na radicale prostatectomie met op nano-MRI ≤ 4 foci met regionale lymfekliermetastasen (maximaal 6 klieren in totaal). |
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E.1.1.1 | Medical condition in easily understood language |
patients with rising PSA-levels after prostate removal with up to 6 lymph node metastases within the pelvis as seen on a nano-MRI scan. |
patiënten met stijgende PSA-waarde na prostaatverwijdering met op een nano-MRI scan maximaal 6 lymfeklieruitzaaiingen in het bekken. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
to evaluate the technical feasibility and efficacy of MR-guided stereotactic body radiotherapy (SBRT) to nano-MRI detected regional lymph node metastases in patients with biochemical recurrent prostate cancer after radical prostatectomy. |
het evalueren van de technische haalbaarheid en effectiviteit van MR-geleide stereotactische radiotherapie op middels nano-MRI gedetecteerde lymfekliermetastasen bij patiënten met biochemisch recidief prostaatcarcinoom na radicale prostatectomie. |
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E.2.2 | Secondary objectives of the trial |
- to determine the tolerability of the abovementioned treatment in terms of acute and late toxicity, both scored according to the Common Terminology Criteria for Adverse Events .
- to determine the radiologic response of abovementioned treatment on repeated nano-MRI’s. |
- bepalen van de tolerantie van bovengenoemde behandeling in termen van acute en late toxiciteit, beide gescoord aan de hand van de Common Terminology Criteria for Adverse Events.
- bepalen van de radiologische respons van bovengenoemde behandeling op herhaalde nano-MRIs. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Biochemical recurrent prostate adenocarcinoma after radical prostatectomy.
- PSA level ≥ 0.2 ng/ml
- No macroscopic disease on PSMA-PET/CT
- No local recurrence on MRI.
- ≤ 4 foci harbouring regional lymph node metastases (up to 6 nodes in total) on nano-MRI (below aortic bifurcation). |
om deel te kunnen nemen aan de studie moeten patiënten aan de volgende criteria voldoen:
- biochemisch recidief prostaatadenocarcinoom na radicale prostatectomie.
- PSA-gehalte ≥ 0.2 ng/ml
- geen macroscopische ziekte op PSMA-PET/CT
- geen lokaal recidief op MRI
- ≤ 4 foci van regionale lymfekliermetastasen (maximaal 6 klieren in totaal) op een nano-MRI (onder de aortabifurcatie). |
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- If any of the inclusion criteria does not apply.
- Concurrent or previous androgen deprivation therapy.
- Previous pelvic radiotherapy.
- Active inflammatory bowel disease (Crohn’s disease or ulcerative colitis).
- Contraindication for MR-imaging according to local Radiology protocol or unable to undergo MR-linac treatment (e.g. due to claustrophobia or body circumference).
- Ferro-magnetic objects in the pelvis or hip causing disturbing susceptibility artifacts (at the discretions of the radiologist).
- Inability to give informed consent.
- Contraindications to Ferrotran as stated in the SPC (including no consent to practice contraception until end of study in case of female partners of childbearing potential). |
Patiënten worden uitgesloten van deelname aan de studie in geval van één of meerdere van onderstaande factoren:
- wanneer aan 1 van de inclusiecriteria niet wordt voldaan.
- concurrente of eerdere androgene deprivatie therapie.
- eerdere radiotherapie in het bekkengebied.
- actieve inflammatoire darmziekte (M. Crohn of colitis ulcerosa).
- contraindicatie voor MRI volgens de lokale protocollen van de Radiologie-afdeling of niet in staat MRI-onderzoek/behandeling te ondergaan (bv vanwege claustrofobie of lichaamsomvang).
- ferromagnetische objecten in het bekken of de heupen, leidend tot verstorende susceptibiliteitsartefacten (naar oordeel van de radioloog).
- niet in staat informed consent te geven.
- contraindicaties voor Ferrotran, zoals beschreven in de SPC (inclusief wanneer, in geval van een vrouwelijke partner in de vruchtbare leeftijd, patiënt niet instemt met anticonceptieve middelen. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main objective of this study is to determine the technical feasibility and efficacy of MRI guided lymph node SBRT in patients with biochemical recurrent prostate cancer after RP and small lymph node metastases on nano-MRI.
- The study approach will be deemed technical feasible when in 90% of patients 1) the nano-MR detected lymph nodes can be objectified on the pre-radiotherapy planning MRI and daily MR-imaging, and 2) as a result can be treated by SBRT according to the set objectives and constraints without excessive > grade 2 treatment related toxicity (i.e. in > 5% of patients).
- Efficacy will measured by the 1-year biochemical control, reflecting disease control. As no formal definition exists for a secondary biochemical relapse, in this study the 1-year biochemical control is defined as a PSA value 1 year after treatment that is < 0.2 ug/l higher than the value at baseline (in case of biochemical relapse confirmation after 6 weeks is needed) |
Het primaire eindpunt van de studie is de technische haalbaarheid en effectiviteit van MR-geleide stereotactische lymfeklierbestraling op middels nano-MRI gedetecteerde lymfekliermetastasen.
- de studiebenadering wordt als technisch haalbaar beschouwd wanneer bij tenminste 90% van de patiënten 1) de middels nano-MRI gedecteerde lymfeklieren kunnen worden geobjectiveerd op de plannings-MRI en de dagelijkse online MRI's en 2) als een gevolg hiervan SBRT op deze klieren kan worden toegepast volgens de hiervoor opgestelde dosislimieten zonder overmatige > graad 2 toxiciteit (dat wil zeggen bij > 5 % van de patiënten).
- effectiviteit zal worden bepaald op basis van de 1-jaars biochemische controle als surrogaat voor ziektecontrole. Aangezien er geen formele definitie bestaat voor een secundair biochemisch recidief wordt in de studie de 1-jaars biochemische controle gedefinieerd als een PSA-waarde < 0.2 ng/l hoger dan de baseline-waarde (in geval van een biochemisch recidief dient dit binnen 6 weken te worden bevestigd middels een herhaalde PSA-meting). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Technical feasibility: this will be determined before and during treatment.
Efficacy: PSA-testing will take place at 3, 6, 9 and 12 (primary endpoint) months after treatment and afterwards according to standard of care. |
Technische haalbaarheid: dit zal voorafgaand en tijdens behandeling worden beoordeeld/bepaald.
Effectiviteit: PSA-metingen vinden plaats op 3, 6, 9 en 12 (primaire eindpunt) maanden na behandeling en nadien volgens standaardzorg. |
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E.5.2 | Secondary end point(s) |
- physician scored acute (until 90 days after treatment) and late toxicity measured by the Common Terminology Criteria for Adverse Events.
- radiologic response of the treated lymph nodes on repeated nano-MRI at 3, 12 and 24 months after treatment will be determined and explorative analyses will be performed to see whether imaging biomarkers are correlated to biochemical outcome. |
- door de behandelend arts gescoorde acute (tot 90 dagen na behandeling) en late toxiciteit gebaseerd op de Common Terminology Criteria for Adverse Events.
- radiologische respons van de behandelde lymfeklieren op herhaalde nano-MRI's na 3, 12 en 24 maanden. Exploratieve analyses zullen worden verricht om potentiele biomarkers te identificeren die gecorreleerd zijn aan biochemische controle. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Toxicity scoring will be performed at baseline, once during treatment, and 6 weeks after treatment, as well as 3, 6, 9, 12, 18, 24, 30 and 36 months after treatment and annually afterwards. The scoring will take place during regular follow-up visits.
- repeated nano-MRI's will be performed at 3, 12 and 24 months after treatment. |
- toxiciteit wordt gescoord op baseline, eenmaal tijdens behandeling en 6 weken, 3, 6, 9, 12, 18, 24, 30, en 36 maanden na behandeling, gevolgd door jaarlijkse controle. Deze score vindt plaats tijdens reguliere follow-up bezoeken.
- herhaalde nano-MRI's vinden plaats 3, 12 en 24 maanden na behandeling. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
single-center, single arm pilot studie |
single-center, single arm pilot study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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1 year after treatment of the final patient included in the trial. Afterwards, regular follow-up will continue according to standard of care. |
1 jaar behandeling van de laatste geincludeerde patiënt. Nadien vindt reguliere follow-up plaats conform standaardzorg. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |