| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Unresectable recurrent, or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) which is positive for human papilloma virus 16 (HPV16+) and expresses PD-L1 |
| Tumore a cellule squamose della testa e del collo (HNSCC) non resecabile, recidivante o metastatico, positivo per il papilloma virus umano 16 (HPV16+) e che esprime PD-L1 |
|
| E.1.1.1 | Medical condition in easily understood language |
| Head and neck cancer positive for human papilloma virus 16 and expressing the protein PD-L1 |
| Tumore testa-collo positivo per il papilloma virus umano 16 e che esprime la proteina PD-L1 |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10060121 |
| E.1.2 | Term | Squamous cell carcinoma of head and neck |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
Safety Run-In Phase (Part A):
- To assess the safety and tolerability profile of BNT113 in combination with pembrolizumab.
Randomized Phase (Part B):
- To demonstrate superiority of BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy in terms of improved OS.
- To assess the anti-tumor activity of BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy according to RECIST 1.1 assessed by BICR.
|
Fase di pre-trattamento (Run-In) di sicurezza (Parte A):
- Valutare il profilo di sicurezza e tollerabilità di BNT113 in combinazione con pembrolizumab.
Fase randomizzata (Parte B):
- Dimostrare la superiorità di BNT113 in combinazione con pembrolizumab rispetto a pembrolizumab in monoterapia in termini di miglioramento dell'OS
- Valutare l'efficacia antitumorale di BNT113 in combinazione con pembrolizumab rispetto a pembrolizumab in monoterapia secondo i criteri RECIST 1.1, valutata dal BICR. |
|
| E.2.2 | Secondary objectives of the trial |
Safety Run-In Phase (Part A):
- To assess the anti-tumor activity of BNT113 in combination with pembrolizumab according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by blinded independent central review (BICR) and by investigators assessment respectively.
Randomized Phase (Part B):
- To assess the anti-tumor activity of BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy according to RECIST 1.1 by investigators assessment.
- To evaluate the efficacy of BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy in terms of PFS according to RECIST 1.1.
- To assess the safety and tolerability profile of BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy.
- To assess health-related quality of life of BNT113 in combination with pembrolizumab compared to pembrolizumab monotherapy.
|
Fase di pre-trattamento (Run-In) di sicurezza (Parte A):
- Valutare l'attività antitumorale di BNT113 in combinazione con pembrolizumab secondo i criteri "Response Evaluation Criteria in Solid Tumors" RECIST 1.1, valutata mediante "Blinded Independent Central Review" (BICR) e l'analisi degli sperimentatori, rispettivamente.
Fase randomizzata (Parte B):
- Valutare l'attività antitumorale di BNT113 in combinazione con pembrolizumab rispetto a pembrolizumab in monoterapia secondo i criteri RECIST 1.1, valutata dallo sperimentatore.
- Valutare l'efficacia di BNT113 in combinazione con pembrolizumab rispetto a pembrolizumab in monoterapia in termini di PFS secondo i criteri RECIST 1.1
- Valutare il profilo di sicurezza e tollerabilità di BNT113 in combinazione pembrolizumab rispetto a pembrolizumab in monoterapia.
- Valutare l'effetto sulla qualità della vita in relazione alla salute di BNT113 in combinazione con pembrolizumab rispetto a pembrolizumab in monoterapia. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Patients must sign the written informed consent form before any screening procedure. Informed consent must be documented before any trial-specific screening procedure is performed.
• Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC that is considered incurable by local therapies.
Note 1: HPV16 positivity in the Safety Run-In Phase (Part A) will be determined using an investigational real time PCR-based (qPCR) test detecting HPV16 E7 DNA derived from FFPE tumor tissue (therascreen HPV RGQ PCR Kit)
Note 2: For the randomized phase (Part B), HPV16 positivity will be determined using an investigational real time PCR-based qPCR test (therascreen HPV Panel RGQ PCR Kit) detecting HPV16 E7 DNA derived from FFPE tumor tissue.
• Patients who have a tumor expressing PD-L1 [CPS =1] as determined by the FDA-approved test PD L1 22C3 pharmDx kit performed and evaluated according to the manufacturer’s specifications.
6. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Patients may not have a primary tumor site of nasopharynx (any histology).
7. Patients must not have had prior systemic anticancer therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to randomization, if given as part of multimodal treatment for locally advanced disease is allowed.
8. Patients who have measurable disease based on RECIST 1.1 as determined by the site and confirmed by BICR. Tumor lesions situated in a previously irradiated area are considered measurable, if progression has been demonstrated in such lesions disease by RECIST 1.1.
9. Patients have Eastern Cooperative Oncology Group (ECOG) performance status =1.
10. Patients have adequate bone marrow function as defined by hematological parameters as described in protocol points a/b/c.
11. Patients have adequate hepatic function, as defined in protocol points a/b.
12. Patients should have adequate kidney function, assessed by the estimated glomerular filtration rate =45 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CPK-EPI) equation Kidney Disease Improving Global Outcomes [KDIGO] 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease; Levey et al. 2009).
13. Patients should be stable with adequate coagulation, as defined in the protocol points a/b.
14. All patients must provide a tumor tissue sample (FFPE blocks/slides) from archival tissue, or fresh biopsy if collected as part of patient’s standard clinical practice before the first dose of trial treatment. The sample should preferably be derived from the primary tumor and from the last tumor sample taken. FFPE block is preferred. If not possible, at least 16 (preferably 20) consecutive slides should be provided. More information about sample quality, requirements, and handling will be provided in a Laboratory Manual.
15. Women of childbearing potential (WOCBP) must have a negative serum (beta-human chorionic gonadotropin) at screening. Patients that are postmenopausal or permanently sterilized can be considered as not having reproductive potential.
16. WOCBP must agree to practice at least one highly effective method of contraception during trial, i.e., starting at screening, during the trial and for at least 90 d after receiving the last dose of BNT113 AND for at least 6 months after receiving the last dose of pembrolizumab.
[...]
Full list is available in the study protocol. |
1. Prima di qualsiasi procedura di screening i pazienti dovranno avere firmato il modulo di consenso informato scritto. Il consenso informato deve essere documentato prima che sia eseguita qualsiasi procedura di screening studio specifica.
2. I pazienti devo avere un età pari o superiore a 18 alla data di firma del consenso informato.
3. I pazienti devono accettare ed essere in grado di seguire le visite programmate, i trattamenti, gli esami di laboratorio, e gli altri requisiti dello studio.
4. Pazienti che presentano HNSCC recidivante o metastatico, HPV16+ confermato istologicamente e ritenuto incurabile con le terapie locali.
Nota 1: la positività per HPV16 nella fase di pre-trattamento di sicurezza (Parte A) sarà determinata usando un test sperimentale basato sulla real time PCR (qPCR) (therascreen HPV RGQ PCR Kit) per la rilevazione del DNA di HPV16 E7 da tessuto tumorale FFPE.
Nota 2: la positività per HPV16 per la fase di randomizzazione (Parte B) sarà determinata usando un test qPCR sperimentale (therascreen HPV Panel RGQ PCR Kit) per la rilevazione del DNA di HPV16 E7 da tessuto tumorale FFPE.
5. Pazienti con un tumore che esprime PD-L1 [CPS =1], determinato dal test con il kit PD-L1 22C3 pharmDx, approvato dall'FDA, eseguito e valutato secondo le specifiche del produttore.
6. Le sedi idonee del tumore primitivo sono l'orofaringe, la cavità orale, ipofaringe e laringe. I pazienti potrebbero non avere una sede del tumore primitivo di rinofaringe (qualsiasi istologia).
7. Pazienti non sottoposti a pregressa terapia antitumorale sistemica somministrata nell'ambito di recidiva o metastasi. È consentita la terapia sistemica completata più di 6 mesi prima della randomizzazione, se somministrata nell’ambito di un trattamento multimodale per malattia localmente avanzata.
8. Pazienti con malattia misurabile in base ai criteri RECIST 1.1, come determinato dal centro e confermato dal BICR. Lesioni tumorali situate in un’area precedentemente irradiata sono considerate misurabili se, per tali lesioni, è stata dimostrata una progressione della malattia secondo i criteri RECIST 1.1.
9. I pazienti hanno l'Eastern Cooperative Oncology Group (ECOG) stato di prestazione =1.
10. I pazienti hanno un'adeguata funzionalità del midollo osseo come definito da parametri ematologici come descritto nei punti del protocollo a / b / c.
11. I pazienti hanno una funzione epatica adeguata, come definita nel protocollo punti a / b.
12. I pazienti devono avere un'adeguata funzionalità renale, valutata dal velocità di filtrazione glomerulare stimata =45 mL / min utilizzando Chronic Kidney Disease Epidemiology Collaboration (CPK-EPI) equazione Rene Disease Improving Global Outcomes [KDIGO] 2012 Clinical Practice Linee guida per la valutazione e la gestione della malattia renale cronica; Levey et al. 2009).
13. I pazienti devono essere stabili con un'adeguata coagulazione, come definito nel protocollo ai punti a / b.
14. Tutti i pazienti devono fornire un campione di tessuto tumorale (blocchetti/vetrini FFPE) da tessuto di archivio o un campione bioptico fresco, se prelevato nell'ambito della pratica clinica standard prima della prima dose del trattamento dello studio. Il campione dovrà essere ottenuto preferibilmente dal tumore primario e dall'ultimo campione bioptico tumorale prelevato. Il blocchetto FFPE è preferibile. Se non fosse possibile, dovranno essere forniti almeno 16 vetrini consecutivi (preferibilmente 20). Maggiori informazioni sulla qualità, sui requisiti e sul trattamento del campione saranno forniti in un documento separato (cioè, il Manuale del laboratorio).
15. Le donne in età fertile (WOCBP) devono avere un siero negativo (gonadotropina corionica beta-umana) allo screening. Pazienti che sono in postmenopausa o sterilizzati permanentemente possono essere considerati come non avere un potenziale riproduttivo.
16. WOCBP deve accettare almeno un metodo altamente efficace di contraccezione [...]
L'elenco completo nel protocollo |
|
| E.4 | Principal exclusion criteria |
1. Patients are pregnant or breastfeeding.
2. Patients present primary tumor site of nasopharynx (any histology).
3. Patients with uncontrolled intercurrent illness as defined in the protocol points a/b/c/d/e/f/ g/h/I/j/k/l/m.
4. Patients with a known allergy, hypersensitivity, or intolerance to BNT113 or its excipients, or to pembrolizumab or its excipients.
5. Patients who have had a splenectomy.
6. Patients who have had major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, or have not fully recovered from surgery, or have a surgery planned during the time of trial participation.
7. Patients who have a known history (testing not required) or has a positive test at screening of any of the following:
a. Human immunodeficiency virus (HIV) 1 or 2.
b. Hepatitis B (carrier or active infection).
c. Hepatitis C (unless considered cured 5 years post curative anti-viral therapy).
8. Patients with another primary malignancy that has not been in complete remission for at least 2 years, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, non-invasive basal or non-invasive squamous cell skin cancer, localized prostate cancer, non-invasive superficial bladder cancer or breast ductal carcinoma in situ).
Note: Any uncertainties should be discussed with the Medical Monitor.
9. Patients with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
10. Patients who have received or currently receive the therapy/medication as defined in the protocol points a/b/c/d/e/f.
11. Prior anti-cancer therapy in the metastatic or in the unresectable recurrent HNSCC setting.
12. Prior treatment with anti-cancer immunomodulating agents, such as blockers of PD 1, PD-L1, tumor necrosis factor receptor superfamily member 9 (TNRSF9, 4 1BB, CD137), OX 40, therapeutic vaccines, cytokine treatments, or any investigational agent within 4 weeks before the first dose of BNT113.
13. Treatment with other anti-cancer therapy including chemotherapy, radiotherapy with curative intent, major surgery with curative intent or biological cancer therapy within 6 months prior to randomization. Adjuvant hormone therapy used for breast cancer in long term remission (refer to Exclusion criterion#8) is allowed.
Note 1: Palliative radiotherapy and palliative surgery are allowed.
Note 2: Prior treatment with bone resorptive therapy, such as bisphosphonates (e.g., pamidronate, zoledronic acid) and denosumab, is allowed assuming that the patients have been on stable doses for =4 weeks prior to first dose of trial treatment.
14. Current evidence of Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) Grade >1 toxicity before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria. Patients with Grade 2 neuropathy may be eligible at Investigator’s discretion.
[...]
Full list is available in the study protocol. |
1. Le pazienti sono incinte o allattano.
2. Pazienti con tumore primitivo di rinofaringe (qualsiasi istologia).
3. Pazienti con malattia intercorrente incontrollata come definita nei punti del protocollo a / b / c / d / e / f / g / h / I / j / k / l / m.
4. Pazienti con allergia, ipersensibilità o intolleranza nota a BNT113 o suoi eccipienti, o a pembrolizumab o suoi eccipienti.
5. Pazienti che hanno subito una splenectomia.
6. Pazienti che hanno subito un intervento chirurgico maggiore (ad es che abbia richiesto un’ anestesia generale) entro 4 settimane prima dello screening o non si sono completamente ripresi
da un intervento chirurgico o hanno pianificato un intervento chirurgico durante il periodo di partecipazione allo studio.
7. Pazienti che hanno una storia nota (test non richiesti) o hanno un test positivo allo screening di uno dei seguenti:
un. Virus dell'immunodeficienza umana (HIV) 1 o 2.
b. Epatite B (portatore o infezione attiva).
c. Epatite C (a meno che non sia considerata guarita 5 anni dopo la cura con terapia antivirale).
8. Pazienti con un altro tumore primario che non è in remissione completa da almeno 2 anni, eccetto i tumori con un rischio trascurabile di metastasi o decesso (quali carcinoma in situ della cervice, carcinoma cutaneo a cellule basali o squamose non invasivo, carcinoma prostatico localizzato, carcinoma superficiale della vescica non invasivo o carcinoma duttale in situ della mammella adeguatamente trattati).
Nota: i casi incerti devono essere discussi con il supervisore medico.
9. Pazienti con qualsiasi condizione per la quale, a parere dello sperimentatore, la partecipazione non sarebbe nel migliore interesse del paziente (ad es., compromettere il benessere) o che potrebbe prevenire, limitare o confondere le valutazioni specificate dal protocollo.
10. Pazienti che hanno ricevuto o attualmente ricevono terapia / farmaco come definito nei punti del protocollo a / b / c / d / e / f.
11. Terapia antitumorale pregressa nell'ambito della cura dell'HNSCC non resecabile ricorrente o metastatico.
12. Trattamento pregresso con agenti immunomodulanti antitumorali, come i bloccanti di PD 1, PD-L1, membro 9 della super-famiglia dei recettori del fattore di necrosi tumorale (TNRSF9, 4 1BB, CD137), OX 40, vaccini terapeutici, trattamenti con citochine o qualsiasi agente sperimentale nelle 4 settimane prima della prima dose di BNT113.
13. Trattamento con altra terapia antitumorale, incluse chemioterapia, radioterapia a scopo curativo, intervento di chirurgia maggiore a scopo curativo o terapia antitumorale biologica nei 6 mesi che precedono la randomizzazione. È consentita la terapia ormonale adiuvante usata per il carcinoma mammario nella remissione a lungo termine (fare riferimento al criterio di esclusione n. 8).
Nota 1: la radioterapia e la chirurgia palliative sono consentite.
Nota 2: trattamento pregresso con terapia con inibitori del riassorbimento osseo, come bifosfonati (per es., pamidronato, acido zoledronico) e denosumab sono consentiti, posto che i pazienti stiano ricevendo dosi stabili da =4 settimane prima della prima dose del trattamento.
14. Evidenza attuale dei criteri terminologici comuni per gli eventi avversi (CTCAE, versione 5.0) Tossicità di grado> 1 prima dell'inizio del trattamento, ad eccezione della caduta dei capelli e di quelle tossicità di Grado 2 elencate come consentite altri criteri di elegibilità. Possono esserlo i pazienti con neuropatia di grado 2
Possono essere idonei a discrezione dello sperimentatore.
[...]
L'elenco completo è disponibile nel protocollo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety Run-In Phase (Part A):
Occurrence of treatment-emergent adverse event (TEAE) assessed according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) including Grade =3, serious, fatal TEAE by relationship
Randomized Phase (Part B):
- Overall Survival (OS) defined as the time from randomization to death from any cause.
- Overall response rate (ORR)
|
Fase di pre-trattamento (Run-In) di sicurezza (Parte A):
-Frequenza di eventi avversi emergenti dal trattamento(Treatment-Emergent Adverse Event, TEAE) valutatisecondo i criteri comuni di terminologia per gli eventiavversi (Common Terminology Criteria for AdverseEvents, CTCAE) versione 5.0 che includono TEAE, digrado =3, gravi, fatali.
Fase randomizzata (Parte B):
- L'OS è definita come il tempo dalla randomizzazione al decesso per qualsiasi causa.
- L'ORR come miglior risposta globale. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs and SAEs: Monitored from signing of the ICF until Safety Follow-Up 2 (SFU2)
Overall Survival (OS): Time from randomization to death from any cause |
AEs e SAEs: Monitorati dalla firma dell' ICF fino al Safety Follow-Up 2 (SFU2)
OS: Periodo di tempo dalla randomizzazione al decesso per ogni causa |
|
| E.5.2 | Secondary end point(s) |
Safety Run-In Phase (Part A):
- Overall response rate (ORR)
- Duration of Response (DoR)
- Disease control rate (DCR)
Randomized Phase (Part B):
- Overall response rate (ORR)
- Progression-Free Survival (PFS)
- Disease control rate (DCR)
- Duration of Response (DoR)
- Occurrence of TEAEs
- Patient-reported outcome (PRO) scores |
Safety Run-In Phase (Part A):
- Overall response rate (ORR)
- Duration of Response (DoR)
- Disease control rate (DCR)
Randomized Phase (Part B):
- Overall response rate (ORR)
- Progression-Free Survival (PFS)
- Disease control rate (DCR)
- Duration of Response (DoR)
- Occurrence of TEAEs
- Patient-reported outcome (PRO) scores |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumor Evaluation: Assessed every 9 (±1) wks for the first 6 months, and then every 12 (±2) wks regardless of any dose delays, until disease progression or until the start of next-line anti-cancer therapy
DOR: Time from first objective response (CR or PR) to first occurrence of objective tumor progression, or death from any cause, whichever occurs first
PFS: Time from randomization to first objective tumor progression, or death from any cause, whichever occurs first.
DCR: Assessed at least 6 weeks after first dose
PRO/QoL assessments: At screening, Start of every cycle till EOT |
Tumor Evaluation: Assessed every 9 (±1) wks for the first 6 months, and then every 12 (±2) wks regardless of any dose delays, until disease progression or until the start of next-line anti-cancer therapy
DOR: Time from first objective response (CR or PR) to first occurrence of objective tumor progression, or death from any cause, whichever occurs first
PFS: Time from randomization to first objective tumor progression, or death from any cause, whichever occurs first.
DCR: Assessed at least 6 weeks after first dose
PRO/QoL assessments: At screening, Start of every cycle till EOT |
|
| 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 | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability, Biomarker Analysis, Immunogenicity |
| Tolerabilità, Analisi dei Biomarker, Immunogenicità |
|
| 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 | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Diversa dose dello stesso prodotto |
| Different dose of the same product |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 85 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Brazil |
| Canada |
| Chile |
| Mexico |
| Russian Federation |
| United States |
| Austria |
| Belgium |
| France |
| Germany |
| Hungary |
| Italy |
| Poland |
| Portugal |
| Spain |
| Sweden |
| United Kingdom |
| Czechia |
| Argentina |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
A patient is considered to have completed the trial if he/she has completed all phases of the trial including survival follow up.
The end of the trial will be declared at the time at which:
• all patients have discontinued trial treatment; and
• all patients have completed the visit Safety Follow-Up 2 (SFU2); and
• the primary and secondary analyses can be performed (i.e., at least 201 OS events have been occurred).
or
• the sponsor discontinues the trial. |
A patient is considered to have completed the trial if he/she has completed all phases of the trial including survival follow up.
The end of the trial will be declared at the time at which:
• all patients have discontinued trial treatment; and
• all patients have completed the visit Safety Follow-Up 2 (SFU2); and
• the primary and secondary analyses can be performed (i.e., at least 201 OS events have been occurred).
or
• the sponsor discontinues the trial. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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