E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic castration-resistant prostate cancer (mCRPC) |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic castration-resistant prostate cancer |
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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 incidence of grade ≥ 3 neutropenia (measured at Day 7 and Day 14) and/or neutropenic complications (febrile neutropenia, neutropenic infection) with two schedules of cabazitaxel (bi-weekly versus tri-weekly) plus prednisone in elderly men (≥ 70 years) with mCRPC previously treated with a docetaxel-containing regimen. |
• Het evalueren van de incidentie van neutropenie van graad ≥3 (gemeten op dag 7 en dag 14) en/of neutropenische complicaties (febriele neutropenie, neutropenische infectie) in twee schema's cabazitaxel (tweewekelijks versus driewekelijks) plus prednison bij bejaarde mannen (≥70 jaar) met mCRPC die eerder behandeld werden met een docetaxelbevattend regime |
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E.2.2 | Secondary objectives of the trial |
The following parameters will be evaluated in each arm: •Dose reductions and dose delays •Radiological progression-free survival (rPFS) •Time to PSA progression •Time to first symptomatic Skeletal-Related Event (SRE) and incidence of SREs •Time to opioid treatment (if relevant) •Prostate-specific antigen (PSA) response rate •Quality of Life (FACT-P) •Objective response rate (ORR) in measurable lesions (RECIST criteria 1.1 – only on metastasis; Appendix G) •Overall Survival (OS) •Factors influencing survival (duration of response to first androgen deprivation therapy (ADT), serum testosterone, cumulative dose of cabazitaxel, neutrophils/lymphocytes ratio, Gleason score, geriatric assessment G8, grade ≥3 neutropenia). •Time to onset of grade ≥3 neutropenia •Grade ≥3 neutropenia duration ( from date of onset of grade ≥ 3 until grade ≤ 2) •Analysis of grade ≥3 neutropenia and/or neutropenia by cycle •Adverse events
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In beide groepen worden de volgende parameters geëvalueerd: •Dosisverlagingen en dosisvertragingen •Radiologische progressievrije overleving (radiological progression-free survival, rPFS) •Tijd tot progressie van PSA •Tijd tot eerste symptomatische skeletgerelateerde voorval (Skeletal-Related Event, SRE) en incidentie van SRE's •Tijd tot opioïdebehandeling (indien relevant) •Responsratio prostaatspecifiek antigeen (PSA) •Kwaliteit van leven (FACT-P) •Objectieve responsratio (ORR) in meetbare laesies (criteria RECIST 1.1 – alleen op metastase; bijlage G) •Totale overleving (overall survival, OS) •Factoren die de overleving beïnvloeden (duur van respons op eerste androgeendeprivatietherapie [ADT], serumtestosteron, cumulatieve dosis cabazitaxel, verhouding neutrofielen/lymfocyten, Gleason-score, geriatrische beoordeling G8, neutropenie van graad ≥3). •Tijd tot ontstaan van neutropenie van graad ≥3
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patient aged ≥ 70 years with mCRPC previously treated with docetaxel 2.Medical or surgical castration with castrate level of testosterone (< 50 ng/dl) 3.Progressive disease according to physician judgement 4.Histologically proven prostate carcinoma 5.Health status allowing use of chemotherapy: G8 > 14; or G8 score ≤ 14 with geriatric assessment concluding to reversible impairment allowing use of chemotherapy 6.ECOG-PS 0, 1 or 2(ECOG-PS= 2 should be related to prostate cancer) 7.Adequate hematologic, liver and renal functions: a)Neutrophil count ≥1.5 109/L b)Haemoglobin ≥10 g/ dL c)Platelet count ≥100.109/L d)Total bilirubin ≤ 1 the upper limit of normal (ULN) e)Transaminases ≤ 1.5 ULN f)Serum creatinine ≤ 2.0 ULN 8.Ongoing LHRH therapy at study entry 9.Signed informed consent
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1. Patiënt ≥70 jaar met mCRPC, eerder behandeld met docetaxel 2. Medische of chirurgische castratie met testosteron op castratieniveau (<50 ng/dl) 3. Progressieve ziekte naar het oordeel van de arts 4. Histologisch aangetoond prostaatcarcinoom 5. Gezondheidstoestand staat gebruik van chemotherapie toe: G8 >14; of G8-score ≤14 met geriatrische beoordeling die concludeert dat er sprake is van omkeerbare beperking die gebruik van chemotherapie toestaat 6. ECOG-PS 0, 1 of 2 (ECOG-PS 2 dient te worden gerelateerd aan prostaatkanker) 7. Adequate hematologische, lever- en nierfunctie: a) Aantal neutrofielen ≥1,5 109/l b) Hemoglobine ≥10 g/dl c) Aantal bloedplaatjes ≥100.109/L d) Totaal bilirubine ≤1 bovengrens van normale waarde (ULN) e) Transaminases ≤ 1,5 ULN f) Serumcreatinine ≤ 2,0 ULN 8. Lopende LHRH-behandeling bij inschrijving in onderzoek 9. Ondertekend informatie- en toestemmingsformulier
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E.4 | Principal exclusion criteria |
1.History of severe hypersensitivity reaction (≥grade 3) to docetaxel 2.History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs 3.Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus) 4.Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix E) 5.ECOG-PS >2 not related to prostate cancer disease 6.G8 ≤ 14 with geriatric assessment contra-indicating standard cabazitaxel regimen 7.Concomitant vaccination with yellow fever vaccine 8.Patient who cannot be regularly followed or cannot answer to quality of life questionnaires because of psychological, social, familial or geographic reasons 9.Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment.
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1. Voorgeschiedenis van ernstige overgevoeligheidsreactie (graad ≥3) op docetaxel 2. Voorgeschiedenis van ernstige overgevoeligheidsreactie (graad ≥3) op polysorbaat 80-bevattende geneesmiddelen 3. Ongecontroleerde ernstige ziekte of medische aandoening (inclusief ongecontroleerde diabetes mellitus) 4. Gelijktijdige of geplande behandeling met krachtige remmers of krachtige opwekkers van cytochroom P450 3A4/5 (een uitwasperiode van één week is noodzakelijk voor patiënten die deze behandelingen al ondergaan) (zie bijlage E) 5. ECOG-PS >2, niet gerelateerd aan prostaatkanker 6. G8 ≤14 met geriatrische beoordeling die contra-indicatief is voor standaard cabazitaxelregime 7. Gelijktijdige vaccinatie met gelekoortsvaccin 8. Patiënt die niet regelmatig kan worden opgevolgd of om psychologische, sociale, familiaire of geografische redenen niet kan antwoorden op vragenlijsten voor kwaliteit van leven. 9. Deelname aan een ander klinisch onderzoek met enig onderzoeksmiddel in de laatste 30 dagen voorafgaand aan inschrijving in het onderzoek.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is: •grade ≥3 neutropenia (measured at D7 and D14 of each cycle) and/or neutropenic complications (febrile neutropenia, neutropenic infection or sepsis) during the overall treatment period |
• Neutropenie van graad ≥3 (gemeten op D7 en D14 van elke cyclus) en/of neutropenische complicaties (febriele neutropenie, neutropenische infectie of sepsis) gedurende de totale behandelingsperiode
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Neutropenia will be measured at D7 and D14 of each cycle |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are: •Dose reductions and dose delays •Radiological progression-free survival (rPFS) •PSA response and time to PSA progression •Time to first symptomatic Skeletal-Related Event (SRE) and incidence of SREs •Time to opioid treatment (if relevant) •Quality of life (FACT-P) •Objective response rate (ORR) in measurable lesions (RECIST) •Overall Survival (OS) •Factors influencing survival (duration of response to first ADT, serum testosterone, cumulative dose of cabazitaxel, neutrophils/lymphocytes ratio, Gleason score, G8, grade ≥3 neutropenia) •Time to onset of grade ≥3 of neutropenia •Grade ≥3 neutropenia duration ( from date of onset of grade ≥ 3 until grade ≤ 2) Analysis of grade ≥3 neutropenia and/or neutropenia by cycle •Adverse events
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• Dosisverlagingen en dosisvertragingen • Radiologische progressievrije overleving (rPFS) • PSA-respons en tijd tot PSA-progressie • Tijd tot eerste symptomatische skeletgerelateerde voorval (SRE) en incidentie van SRE's • Tijd tot opioïdebehandeling (indien relevant) • Kwaliteit van leven (FACT-P) • Objectieve responsratio (ORR) in meetbare laesies (RECIST) • Totale overleving (OS) • Kwaliteit van leven (FACT-P) • Factoren die de overleving beïnvloeden (duur van respons op eerste ADT, serumtestosteron, cumulatieve dosis cabazitaxel, verhouding neutrofielen/lymfocyten, Gleason-score, G8, neutropenie van graad ≥3) • Tijd tot ontstaan van neutropenie van graad ≥3 • Duur van neutropenie van graad ≥3 (van datum van ontstaan van graad ≥3 tot graad ≤2) Analyse van neutropenie van graad ≥3 en/of neutropenie per cyclus • Bijwerkingen
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For the 2 arms (A and B): -tumor evaluation (CT-Scan abdominal/pelvic/chest or whole body MRI and Bone scan): every 3 months -PSA, FACT-P, pain status (VAS), SRE: at each visit -hematology: every week |
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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 | No |
E.6.4 | Safety | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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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The study will end after the last patient included completed all the evaluation required |
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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 | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |