Clinical Trials Register

Summary
EudraCT Number:	2017-004397-34
Sponsor's Protocol Code Number:	D933KC00001
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-05-15
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2017-004397-34

A.3

Full title of the trial

A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Given Concurrently with Platinum-based Chemoradiation Therapy in Patients with Locally Advanced, Unresectable Non-small Cell Lung Cancer (Stage III) (PACIFIC2)

Globalne, wieloośrodkowe, badanie III fazy, prowadzone z zastosowaniem metodyki podwójnie ślepej próby i randomizacji, kontrolowane placebo, z durwalumabem podawanym równocześnie z chemioradioterapią opartą na pochodnych platyny, u pacjentów z miejscowo zaawansowanym, nieoperacyjnym niedrobnokomórkowym rakiem płuc (stopień III) (PACIFIC2)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of durvalumab/placebo + chemoradiation Therapy in Patients with Locally Advanced Non-small Cell Lung Cancer

Badanie oceniające leczenie z zastosowaniem durwalumabu/placebo podawanego równocześnie z chemioradioterapią, u pacjentów z miejscowo zaawansowanym, nieoperacyjnym niedrobnokomórkowym rakiem płuc

A.3.2

Name or abbreviated title of the trial where available

PACIFIC2

A.4.1

Sponsor's protocol code number

D933KC00001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Study Information Center
B.5.3	Address:
B.5.3.1	Street Address	Karlebyhus, Astraallén
B.5.3.2	Town/ city	Södertälje
B.5.3.3	Post code	SE 151 85
B.5.3.4	Country	Sweden
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	durvalumab
D.3.2	Product code	MEDI4736
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	durvalumab
D.3.9.1	CAS number	1428935-60-7
D.3.9.2	Current sponsor code	MEDI4736
D.3.9.3	Other descriptive name	DURVALUMAB
D.3.9.4	EV Substance Code	SUB176342
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Poland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Cisplatin
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Cisplatin
D.3.9.1	CAS number	15663-27-1
D.3.9.3	Other descriptive name	CISPLATIN
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Poland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Carboplatin
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carboplatin
D.3.9.1	CAS number	41575-94-4
D.3.9.3	Other descriptive name	Carboplatin
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Poland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Pemetrexed
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PEMETREXED
D.3.9.1	CAS number	137281-23-3
D.3.9.3	Other descriptive name	PEMETREXED
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Poland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Etoposide
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ETOPOSIDE
D.3.9.1	CAS number	33419-42-0
D.3.9.3	Other descriptive name	ETOPOSIDE
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 6
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.2	Country which granted the Marketing Authorisation	Poland
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Paclitaxel
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Paclitaxel
D.3.9.1	CAS number	33069-62-4
D.3.9.3	Other descriptive name	Paclitaxel
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Locally Advanced, Unresectable Non-small Cell Lung Cancer (Stage III)

Pacjenci z miejscowo zaawansowanym, nieoperacyjnym Niedrobnokomórkowym Rakiem Płuca (stadium III)

E.1.1.1

Medical condition in easily understood language

Specific type of lung cancer called “Non-Small Cell Lung Cancer” (NSCLC) that cannot be removed by surgery

Specyficzny typ raka płuca nazywanym „niedrobnokomórkowym rakiem płuca” (NDRP), który nie może być usunięty operacyjnie

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10029515
E.1.2	Term	Non-small cell lung cancer recurrent
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of durvalumab + Standart of care (SoC) chemoradiation therapy (CRT) compared with placebo + SoC CRT in terms of Progression Free Survival (PFS) and objective response rate (ORR)

Ocena skuteczności leczenia durwalumabem + standardową chemioradioterapią (SoC CRT) w porównaniu z placebo + SoC CRT pod względem czasu przeżycia bez progresji choroby (PFS) i odsetka odpowiedzi obiektywnych (ORR)

E.2.2

Secondary objectives of the trial

Assess the efficacy of durvalumab+SoC CRT compared with placebo+SoC CRT in terms of :
-Overall Survival (OS)
-Rate of Complete Response (CR)
-Duration of Response (DoR)
-Disease Control Rate (DCR)
-Time from randomization to second progression (PFS2)
-Time to death or distant metastasis (TTDM)

Pharmacokinetics (PK) of Durvalumab when in combination with CRT.
Immunogenicity of Durvalumab +/- in combination with CRT
Effect of Durvalumab+ SoC CRT compared with placebo on subjects disease-related symptoms and health related quality of life (HRQoL)
Safety Objective

Ocena skuteczności durwalumabu + SoC CRT w porównaniu z placebo + SoC CRT pod względem parametrów:
•przeżycie całkowite (OS),
• odsetek pacjentów pozostających przy życiu 24 miesiące od randomizacji (OS24),
• odsetek odpowiedzi całkowitej (CR),
• czas trwania odpowiedzi (DoR),
• odsetek kontroli choroby (DCR),
• czas od randomizacji do drugiej progresji (PFS2),
• czas do wystąpienia zgonu albo przerzutu odległego (TTDM)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Subjects with histologically- or cytologically-documented NSCLC
- Locally advanced or metastatic, unresectable (Stage III) NSCLC
- World Health Organisation (WHO) performance status 0-1
- At least one measurable lesion, not previously irradiated
- Must have a life expectancy of at least 12 weeks at randomization

• Udokumentowany histologicznie lub cytologicznie niedrobnokomórkowy rak płuca (NDRP)
• Miejscowo zaawansowany lub z przerzutami, nieoperacyjny (stopień III) NDRP
• Stan sprawności wg skali Światowej Organizacji Zdrowia (WHO)/Eastern Cooperative Oncology Group (ECOG) 0 lub 1
• Pacjenci z co najmniej jedną zmianą, która nie była wcześniej naświetlana
• Oczekiwany czas przeżycia musi wynosić co najmniej 12 tygodni podczas randomizacji

E.4

Principal exclusion criteria

- Receipt of prior or current cancer treatment, including but not limited to, radiation therapy, investigational agents, chemotherapy, Durvalumab and mAbs.
- Prior exposure to immune-mediated therapy, including but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti PD L2 antibodies, excluding therapeutic anticancer vaccines.

- History of allogeneic organ transplantation
- Active or prior documented autoimmune or inflammatory disorders
- Uncontrolled intercurrent illness
- History of another primary malignancy / leptomeningeal carcinomatosis / active primary immunodeficiency
- Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
- Mixed small cell and NSCLC histology
- Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling
- Known allergy or hypersensitivity to any of the IPs or any of the IP excipients.
- Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥20 Gy in total (V20) of more than 35% of lung volume.

• Wcześniejsze lub aktualne leczenie przeciwnowotworowe, w tym m.in. radioterapia, leki o charakterze eksperymentalnym, chemioterapia, durwalumab i przeciwciała monoklonalne
• Stosowanie wcześniej leczenia immunologicznego, w tym w szczególności innych przeciwciał anty CTLA 4, anty PD 1, anty PD L1 i anty PD L2, z wyłączeniem leczniczych szczepionek przeciwnowotworowych
• Przebyte allogeniczne przeszczepienie narządu
• Udokumentowane aktywne lub wcześniej przebyte choroby autoimmunologiczne lub zapalne
• Niekontrolowane choroby współistniejące
• W wywiadzie - Inny pierwotny nowotwór złośliwy, zajęcia przez nowotwór opon miękkich, aktywny pierwotny niedobór odporności
• Aktywna faza zakażenia, w tym gruźlica, wirusowe zapalenie wątroby typu B, wirusowe zapalenie wątroby typu C lub zakażenie ludzkim wirusem niedoboru odporności
• Typ histologiczny: mieszany drobnokomórkowy i niedrobnokomórkowy rak płuca
• Jakiekolwiek przeciwwskazania medyczne do stosowania dwulekowej chemioterapii na bazie platyny wymienione w lokalnych drukach informacyjnych
• Stwierdzona alergia lub nadwrażliwość na którykolwiek z produktów badanych lub substancji pomocniczych wchodzących w skład produktów badanych
• Pacjenci, w przypadku których w ramach planowanej radioterapii prawdopodobnie ponad 35% objętości płuca otrzyma łącznie dawkę ≥20 Gy (V20).

E.5 End points

E.5.1

Primary end point(s)

PFS using BICR assessments according to RECIST 1.1
ORR using BICR assessments according to RECIST 1.1

PFS przy użyciu ocen BICR, zgodnie z kryteriami RECIST 1.1
ORR przy użyciu ocen BICR, zgodnie z kryteriami RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

On-study tumor assessments begin at Baseline, then 16 weeks ±1w after randomization and continue q8w ±1w through 48 weeks (relative to the date of randomization) and then q12w ±1w thereafter (relative to the date of randomization) until RECIST 1.1-defined radiological progression plus an additional regularly scheduled follow-up scan.

Ocena guza w badaniu rozpoczyna się od danych wyjściowych, następnie 16 tygodni ±1 tydzień po randomizacji i jest kontynuowana co 8 tygodni ±1 tydzień do tygodnia 48 (stosownie do daty randomizacji) i następnie co 12 tygodni ±1 tydzień, od tego czasu (stosownie do daty randomizacji) do wystąpienia zdefiniowanej kryteriami RECIST 1.1 progresji radiologicznej - plus dodatkowy regularnie zaplanowany skan kontrolny.

E.5.2

Secondary end point(s)

OS and OS24
Rate of CR, DoR, DCR, and TTDM using BICR assessments according to RECIST 1.1
PFS2 as defined by local standard clinical practice
Concentration of durvalumab in blood (such as peak and trough concentration, as data allow; sparse sampling)
ADA (confirmatory results: positive or negative; titers [ADA neutralizing antibodies will also be assessed])
Presence of ADA for durvalumab (confirmatory results: positive or negative; titers)
EORTC QLQ-C30 and QLQ-LC13: Change in symptoms, functioning, and global health status/QoL
Safety assessment

• OS i OS24
• Odsetek CR, DoR, DCR i TTDM przy użyciu ocen BICR, zgodnie z kryteriami RECIST 1.1
• PFS2 według definicji ujętej w lokalnych zasadach standardowej praktyki klinicznej
• Stężenie durwalumabu we krwi (np. maksymalne i minimalne stężenie, na ile pozwolą na to dane, na podstawie wybiórczo pobieranych próbek)
• Przeciwciało przeciwlekowe, ADA (wyniki potwierdzające: dodatni lub ujemny; miana [oceniane będą również przeciwciała neutralizujące ADA, ])
• Obecność ADA przeciwko durwalumabowi (wynik potwierdzający: dodatni lub ujemny; miana)
• Kwestionariusze EORTC QLQ-C30 oraz QLQ-LC13: zmiana dotycząca objawów, funkcjonowania i ogólnego stanu zdrowia/jakości życia
• Ocena bezpieczeństwa

E.5.2.1

Timepoint(s) of evaluation of this end point

Rate of CR, DoR, DCR, and TTDM (BICR RECIST 1.1): Tumor assessments at Baseline, then 16w ±1w, then q8w ±1w through 48w and then q12w ±1w thereafter until PD (+1follow-up scan)
OS, OS24 - Patient level: Assessments every 4w during treatment period and every 8w post IP discontinuation until the end of the study or ICF withdrawn. additional contacted in the week following data cutoff to confirm survival status. ADA will be collected at cycle 1, 2 and 4. ePRO : screening, then on 2, 4, 6, 8, 12, 16, and 20w after first dose of IP, then q8w ±1w through 52 weeks and then q12w ±1w until PD or IP discontinuation, at PD or IP discontinuation, and at 8 and 16 weeks after PD or IP discontinuation

Odsetek CR, DoR, DCR, i TTDM (wg BICR RECIST 1.1): ocena guza – dane wyjściowe, następnie w tyg. 16 ±1 tydz, później co 8 tyg. ±1 tydz. do tyg. 48 i następnie co 12 tyg. ±1 tydz. , aż do PD (+ jeden skan kontrolny)
OS, OS24 odsetek pacjentów – co 4 tyg. w okresie aktywnego leczenia i co 8 tyg. po zaprzestaniu leczenia, do zakończenia badania lub wycofania zgody; dodatkowy kontakt w tygodniu po terminie odcięciu danych w celu potwierdzenia statusu przeżycia.
ADA- w cyklach 1, 2 i 4.
ePRO: w fazie przesiewowej, w tyg. 2, 4, 6, 8, 12, 16 i 20 po pierwszej dawce IP, następnie co 8 tyg. ±1 tydz. do tyg. 52 i co 12 tyg. ±1 tydz. do PD lub zaprzestaniu leczenia, w chwili wystąpienia PD lub zaprzestania leczenia oraz w 8 i 16 tyg. po PD lub zaprzestaniu leczenia.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability
Healthcare resource utilization
Quality of life

Tolerancja
Wykorzystanie zasobów opieki zdrowotnej
Jakość życia

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Brazil

India

Japan

Korea, Republic of

Mexico

Peru

Philippines

Russian Federation

Thailand

Turkey

Ukraine

Vietnam

Hungary

Poland

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

The end of study is defined as the last expected visit/contact of the last patient undergoing the study.
A patient is considered to have completed the study when he/she has completed his/her last scheduled visit or last scheduled procedure.

Zakończenie badania zdefiniowano jako ostatnią przewidzianą wizytę/kontakt z ostatnim pacjentem uczestniczącym w badaniu.
Uważa się, że pacjent zakończył udział w badaniu, kiedy zakończona została ostatnia wizyta lub ostatnia procedura przewidziana harmonogramem badania.

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

234

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

156

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

A legal representative may provide consent on behalf of a subject incapable of giving consent personally, where permitted by local regulations.

Zgodnie z lokalnymi przepisami Przedstawiciel Prawny może udzielić zgody w imieniu pacjenta niezdolnego do samodzielnego wyrażenia zgody.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

390

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

AstraZeneca will continue to supply treatment to patients as per CSP, until confirmed PD, unacceptable toxicity, or any of the discontinuation criteria are met.

AstraZeneca będzie dostarczać pacjentom leczenie zgodne z protokołem, do momentu wystąpienia potwierdzonej progresji, przypadku niedopuszczalnej toksyczności lub spełnienia któregokolwiek z kryteriów wyłączenia.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-06-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-18

P. End of Trial
P.	End of Trial Status	Ongoing

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