| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| This study will enroll patients with histologically or cytologically confirmed adenocarcinoma of the pancreas that is metastatic (Stage IV). |
| Il presente studio arruolerà pazienti affetti da adenocarcinoma del pancreas, istologicamente o citologicamente confermato, in fase metastatica (stadio IV). |
|
| E.1.1.1 | Medical condition in easily understood language |
| Metastatic pancreatic adenocarcinoma (PDAC) |
| Adenocarcinoma pancreatico metastatico (PDAC) |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033599 |
| E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033610 |
| E.1.2 | Term | Pancreatic carcinoma metastatic |
| 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 |
| To compare overall survival (OS) of patients with metastatic pancreatic adenocarcinoma (PDAC) treated with BBI-608 plus weekly nab-paclitaxel with gemcitabine (Arm 1) versus weekly nab-paclitaxel with gemcitabine (Arm 2). |
| Confrontare la sopravvivenza complessiva (OS) di pazienti affetti da adenocarcinoma pancreatico metastatico (PDAC) trattati con BBI-608 più somministrazione settimanale di nab-paclitaxel con gemcitabina (Braccio 1) rispetto alla somministrazione settimanale di nab-paclitaxel con gemcitabina (Braccio 2). |
|
| E.2.2 | Secondary objectives of the trial |
To compare OS in patients treated with BBI-608 plus weekly nabpaclitaxel with gemcitabine (Arm 1) versus weekly nab-paclitaxel with gemcitabine (Arm 2) in biomarker positive PDAC patients.
To compare Progression-Free Survival in patients with metastatic PDAC treated with BBI-608 plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine.
To compare PFS in patients with metastatic PDAC treated with BBI-608 plus weekly nab-paclitaxel with gemcitabine versus weekly nabpaclitaxel with gemcitabine in biomarker positive patients.
To compare Overall Response Rate and Disease Control Rate in patients with metastatic PDAC treated with BBI-608 plus weekly nab-paclitaxel with gemcitabine versus weekly nab-paclitaxel with gemcitabine.
To compare ORR and DCR in patients with metastatic PDAC treated
To evaluate the safety profile of BBI-608
To compare the Quality of Life (QoL). |
Confrontare l’OS in pz trattati con BBI-608 più somministraz sett di nab-paclitaxel con gemcitabina (Braccio 1) rispetto alla somministraz sett di nab-paclitaxel con gemcitabina (Braccio 2) in pz affetti da PDAC con biomarcatori positivi.
Confrontare la PFS in pz affetti da PDAC metastatico trattati con BBI-608 più somministraz sett di gemcitabina rispetto alla somministraz sett di nab-paclitaxel con gemcitabina.
Confrontare la PFS in pz affetti da PDAC metastatico trattati con BBI-608 più somministraz sett di nab-paclitaxel con gemcitabina rispetto alla somministraz sett di nab-paclitaxel con gemcitabina in pz con biomarcatori positivi.
Confrontare ORR e DCR in pz affetti da PDAC metastatico trattati con BBI-608 più somministraz sett di nab-paclitaxel con gemcitabina rispetto alla somministraz sett di nab-paclitaxel con gemcitabina.
Confrontare l’ORR il DCR in pz affetti da PDAC metastatico trattati
Valutare il profilo di sicurezza di BBI-608
Confrontare la qualità della vita (QoL). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
This study will enroll patients with histologically or cytologically confirmed adenocarcinoma of the pancreas that is metastatic (Stage IV).
Patients with local recurrence following surgical resection will be excluded. At randomization, patients will have been diagnosed = or < 6 weeks prior to randomization and will not have received systemic
chemotherapy for metastatic pancreatic adenocarcinoma previously (with a fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting allowed). Other inclusion criteria for all patients include: age ≥ 18 years; ECOG performance status ≤ 1; and adequate hepatic, renal, and bone-marrow function. |
| Il presente studio arruolerà pazienti affetti da adenocarcinoma del pancreas, istologicamente o citologicamente confermato, in fase metastatica (stadio IV). Saranno esclusi i pazienti con recidiva locale in seguito a resezione chirurgica. Alla randomizzazione, i pazienti dovranno aver ricevuto la diagnosi ≤6 settimane prima della randomizzazione e non dovranno aver ricevuto precedentemente chemioterapia sistemica per adenocarcinoma pancreatico metastatico (con una fluoropirimidina o gemcitabina somministrata come radio-sensibilizzante nel contesto adiuvante consentito). Altri criteri di inclusione per tutti i pazienti includono: età ≥18 anni, stato di validità secondo il Gruppo cooperativo orientale di oncologia (ECOG) ≤1 e adeguata funzionalità epatica, renale e del midollo osseo. |
|
| E.4 | Principal exclusion criteria |
-Patients with no evidence of metastatic disease as well as patients with a local recurrence following surgical resection of primary lesion.
-Patient has experienced a decline in ECOG performance status between Baseline visit and within 72 hours prior to randomization.
-Patient has a > or = 20% decrease in serum albumin level between Baseline visit and within 72 hours prior to randomization.
-Any prior anti-cancer chemotherapy, biologic or investigational therapy for PDAC.
-Major surgery within 4 weeks prior to randomization.
-Any known brain or leptomeningeal metastases are excluded, even if treated.
-Patients with clinically significant ascites.
-Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of BBI-608 or while undergoing treatment with nab-paclitaxel and
gemcitabine and for 180 days after the last dose of nab-paclitaxel and gemcitabine.
-Gastrointestinal disorder(s) which, in the opinion of the Principal Investigator, would significantly impede the absorption of an oral agent (e.g. active Crohn's disease, ulcerative colitis, extensive gastric and
small intestine resection).
-Unable or unwilling to swallow BBI-608 capsules daily.
-Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds,
symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness
of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
-Known hypersensitivity to gemcitabine, taxanes or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the
product or comparator SmPC or Prescribing Information.
-Neurosensory neuropathy > or = grade 2 at baseline.
-Abnormal glucuronidation of bilirubin, known Gilbert's syndrome.
-Uncontrolled chronic diarrhea > or = grade 2 at baseline.
-Patients being treated with Warfarin.
-Patients with active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy
-Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated by surgery alone or surgery plus radiotherapy with no evidence of disease continuously for > or = 5 years.
-Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
-Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol, including patients with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol. Patients planning to take a vacation for 7 or
more consecutive days during the course of the study are ineligible.
|
-Pazienti senza alcuna evidenza di malattia metastatica, nonché pazienti con recidiva locale a seguito di resezione chirurgica della lesione primaria.
-Pazienti che hanno manifestato un declino dello stato di validità ECOG tra la Visita basale ed entro 72 ore prima della randomizzazione.
-Pazienti con una riduzione > o =20% nel livello di albumina sierica tra la Visita basale ed entro 72 ore prima della randomizzazione.
-Qualsiasi chemioterapia antitumorale pregressa, terapia biologica o sperimentale per il PDAC.
-Intervento di chirurgia maggiore nelle 4 settimane precedenti la randomizzazione.
-È esclusa qualsiasi metastasi cerebrale o leptomeningea nota, anche se trattata.
-Pazienti con ascite clinicamente significativa.
-Donne in gravidanza o allattamento. Le donne non devono allattare al seno mentre assumono il trattamento dello studio e nelle 4 settimane successive all’ultima dose di BBI-608, o durante il trattamento con nab-paclitaxel e gemcitabina e nei 180 giorni successivi all’ultima dose di nab-paclitaxel e gemcitabina.
-Patologia/e gastrointestinale/i che, a giudizio dello sperimentatore principale, impedirebbe/impedirebbero significativamente l’assorbimento di un agente orale (ad es., malattia di Crohn attiva, colite ulcerosa, resezione gastrica e dell’intestino tenue estensiva).
-Incapacità o riluttanza a deglutire le capsule di BBI-608 ogni giorno.
-Malattia intercorrente non controllata, comprese, a titolo esplicativo ma non esaustivo, infezione in corso o attiva, ferite clinicamente significative più o meno in via di guarigione, insufficienza cardiaca congestizia sintomatica, angina pectoris instabile, aritmia cardiaca clinicamente significativa, malattia polmonare significativa (respiro affannoso a riposo o sotto lieve sforzo fisico), infezione non controllata o malattia psichiatrica/situazioni sociali che limiterebbero la conformità ai requisiti dello studio.
-Ipersensibilità nota a gemcitabina, tassani o uno qualsiasi dei loro eccipienti, oppure insorgenza di uno qualsiasi degli eventi specificati nelle sezioni Controindicazioni o Avvertenze e precauzioni speciali riportate nel Riassunto delle caratteristiche del prodotto (RCP) o nelle Informazioni di prescrizione del prodotto o del comparatore.
-Neuropatia neurosensoriale > o di grado =2 al basale.
-Glucuronidazione anomala della bilirubina, sindrome di Gilbert nota.
-Diarrea cronica non controllata di grado > o =2 al basale.
-Pazienti trattati con warfarin.
-Pazienti con una o più infezioni batteriche, virali o micotiche attive e non controllate che richiedono una terapia sistemica.
-Pazienti con anamnesi di altri tumori maligni, esclusi: carcinoma cutaneo non melanoma adeguatamente trattato, carcinoma in situ della cervice trattato con intento curativo o altri tumori solidi trattati con intento curativo mediante sola chirurgia o chirurgia associata a radioterapia senza alcuna evidenza di malattia ininterrottamente per > o =5 anni.
-Qualsiasi condizione patologica attiva che renderebbe pericoloso il trattamento del protocollo o comprometterebbe la capacità del paziente di ricevere la terapia prevista dal protocollo.
-Qualsiasi condizione (ad es., fisiologica, geografica, ecc.) che non consenta la conformità al protocollo, compresi quei pazienti con anamnesi di scarsa conformità o anamnesi di abuso di farmaci/alcol o eccessivo consumo di bevande alcoliche che interferirebbe con la capacità di attenersi al protocollo dello studio. Non sono idonei quei pazienti che prevedono di andare in vacanza per ≥7 giorni consecutivi durante il corso dello studio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary study endpoint is Overall Survival (OS), defined as the time
from randomization until death from any cause. The study is designed to
have a power of 90% and a two-sided alpha of 5% to detect a 20%
reduction in the continuous risk of death (HR 0.80, which corresponds to
an increase of median survival from 8.5 to 10.63 months) in the
Intention to Treat (ITT) general study population. |
The primary study endpoint is Overall Survival (OS), defined as the time
from randomization until death from any cause. The study is designed to
have a power of 90% and a two-sided alpha of 5% to detect a 20%
reduction in the continuous risk of death (HR 0.80, which corresponds to
an increase of median survival from 8.5 to 10.63 months) in the
Intention to Treat (ITT) general study population. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
It is estimated that 864 events will be required to detect this reduction
which would be observed by randomizing 1132 patients enrolled over 24
months with patient follow up for an additional 12 months, for total
study duration of 36 months. It is anticipated that up to 5% dropout rate
will occur for the entire study. |
It is estimated that 864 events will be required to detect this reduction
which would be observed by randomizing 1132 patients enrolled over 24
months with patient follow up for an additional 12 months, for total
study duration of 36 months. It is anticipated that up to 5% dropout rate
will occur for the entire study. |
|
| E.5.2 | Secondary end point(s) |
-All randomized patients will be included in the analysis of PFS, which is
defined as the time interval between the date of randomization and the
date of objective disease progression or death, whichever comes first. If
neither event has been observed, then the patient will be censored at
the date of the last tumor assessment. The date of disease progression is
defined as the date when the criteria for objective progression are first
met.
-Patients with measurable disease by RECIST 1.1 at randomization will
be included in the analysis of ORR which is defined as a composite of
Partial Response and Complete Response as classified according to the
definitions set out below (Eisenhauer, 2009).
-Patients who have measurable disease by RECIST 1.1 at randomization
will be included in the analysis of DCR which is defined as a composite of
Stable Disease, Partial Response and Complete Response as classified
according to the definitions set out below (Eisenhauer, 2009).
-All patients who have completed the baseline quality of life
questionnaire and at least one other QoL questionnaire are evaluable. |
-All randomized patients will be included in the analysis of PFS, which is
defined as the time interval between the date of randomization and the
date of objective disease progression or death, whichever comes first. If
neither event has been observed, then the patient will be censored at
the date of the last tumor assessment. The date of disease progression is
defined as the date when the criteria for objective progression are first
met.
-Patients with measurable disease by RECIST 1.1 at randomization will
be included in the analysis of ORR which is defined as a composite of
Partial Response and Complete Response as classified according to the
definitions set out below (Eisenhauer, 2009).
-Patients who have measurable disease by RECIST 1.1 at randomization
will be included in the analysis of DCR which is defined as a composite of
Stable Disease, Partial Response and Complete Response as classified
according to the definitions set out below (Eisenhauer, 2009).
-All patients who have completed the baseline quality of life
questionnaire and at least one other QoL questionnaire are evaluable. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
All patients will have their BEST RESPONSE from the start of study
treatment until the end of treatment. Tumor assessments will be
performed every 8 weeks after randomization until objective disease
progression or treatment discontinuation due to toxicity. |
All patients will have their BEST RESPONSE from the start of study
treatment until the end of treatment. Tumor assessments will be
performed every 8 weeks after randomization until objective disease
progression or treatment discontinuation due to toxicity. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Efficacy Quality of Life |
| Efficacia sulla Qualità della Vita |
|
| 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 102 |
| 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 |
| Austria |
| Belgium |
| Canada |
| China |
| Czech Republic |
| Denmark |
| France |
| Germany |
| Italy |
| Japan |
| Korea, Republic of |
| Netherlands |
| Poland |
| Portugal |
| Russian Federation |
| Singapore |
| Spain |
| Sweden |
| Taiwan |
| Ukraine |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
