Clinical Trials Register

Summary
EudraCT Number:	2015-002934-32
Sponsor's Protocol Code Number:	D4884C00001
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-15
Trial results	View 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

2015-002934-32

A.3

Full title of the trial

A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients with Advanced Solid Tumors

Wieloośrodkowe, prowadzone metodą próby otwartej, badanie kliniczne fazy II oceniające zastosowanie Tremelimumabu w monoterapii u pacjentów z rozpoznaniem zaawansowanych guzów litych

A.3.1

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

A study to see if experimental anti-cancer medicines Tremelimumab, or MEDI4736 or their combination can keep cancer from growing and the safety of these drugs.

Badanie oceniające, czy eksperymentalne leki przeciwnowotworowe Tremelimumab lub MEDI4736, lub ich kombinacja, mogą powstrzymać wzrost guza i oceniające również bezpieczeństwo tych produktów.

A.3.2

Name or abbreviated title of the trial where available

Tremelimumab_CTLA4_Basket

A.4.1

Sponsor's protocol code number

D4884C00001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02527434

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	AstraZenenca 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	AstraZenenca 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	Information Center
B.5.3	Address:
B.5.3.1	Street Address	1800 Concord Pike, PO Box 15437
B.5.3.2	Town/ city	Wilminton
B.5.3.3	Post code	19850-5437
B.5.3.4	Country	United States
B.5.4	Telephone number	0018002369933
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	Tremelimumab
D.3.2	Product code	MEDI1123
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	Tremelimumab
D.3.9.1	CAS number	745013-19-6
D.3.9.2	Current sponsor code	MEDI1123
D.3.9.3	Other descriptive name	MEDI1123
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	20
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	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	MEDI4736
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.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Adult patients (age ≥18 years) with advanced and metastatic solid tumors including but not limited to histologically or cytologically documented UBC, PDAC, or TNBC.

Dorośli pacjenci (w wieku ≥18 lat) z zaawansowanym lub przerzutowym guzem litym, w tym między innymi histologicznie lub cytologicznie potwierdzonym UBC, PDAC lub TNBC.

E.1.1.1

Medical condition in easily understood language

Urothelial bladder cancer /Triple-negative breast cancer /Pancreatic ductal adenocarcinoma

Urotelialny rak pęcherza moczowego (UBC) / Potrójnie negatywny rak piersi (TNBC) / Gruczolakorak przewodowy trzustki (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	19.0
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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10071664
E.1.2	Term	Bladder transitional cell carcinoma 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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10075566
E.1.2	Term	Triple negative breast cancer
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

Objective response rate (ORR) of tremelimumab monotherapy

Ocena skuteczności tremelimumabu w monoterapii pod względem odsetka odpowiedzi obiektywnych (ORR)

E.2.2

Secondary objectives of the trial

1. To further assess the efficacy of tremelimumab monotherapy.
2. To assess the efficacy of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy.

1. Dalsza ocena skuteczności tremelimumabu w monoterapii
2. Ocena skuteczności MEDI4736 w monoterapii lub leczenia skojarzonego MEDI4736 + tremelimumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥18 years at the time of screening
2. Written informed consent and any locally required authorization
3. Patients affected by histologically or cytologically documented solid tumor malignancies, including but not limited to 1 of the following:
-UBC
-Metastatic PDAC
-TNBC.
- Are intolerant, are ineligible for, or have refused treatment with standard first-line therapy
4. Willing to give valid written consent to provide a tumor biopsy, archival or fresh (preferred), for the purpose of establishing PD-L1 status and for exploratory biomarker analyses
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scans, preferably with IV contrast, and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. Lesions in a previously irradiated field can be used as measurable disease provided that there has been demonstrated progression in the lesion.
7.No prior exposure to immune-mediated therapy, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines.
8. Adequate organ and marrow function
9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.</

1.Wiek ≥18 lat podczas oceny przesiewowej
2.Świadoma zgoda w postaci pisemnej oraz wymagane lokalnie zezwolenie
3.Pacjenci z histologicznie lub cytologicznie potwierdzonym litym nowotworem złośliwym, obejmującym 1 z poniższych, ale nie wyłącznie
• UBC
• PDAC z przerzutami
• TNBC
• Nie tolerują, nie kwalifikują się do lub odmówili poddania się standardowemu leczeniu pierwszego rzutu
4.Są skłonni wyrazić wiążącą, pisemną zgodę na wykonanie biopsji guza, wynik archiwalny lub świeża biopsja (preferowane) dla potrzeb określenia ekspresji PD-L1 oraz badawczych analiz markerów biologicznych
5.Stan sprawności w momencie włączenia do badania wynoszący 0 lub 1 według Wschodniej Grupy Współpracy Onkologicznej (ECOG).
6.Obecność, co najmniej 1 zmiany, nie poddawanej wcześniejszej radioterapii, której największy wymiar, dokładnie zmierzony w badaniu tomografii komputerowej (TK) (preferowane) lub rezonansu magnetycznego (MRI), najlepiej po podaniu kontrastu, wynosi wyjściowo ≥10 mm (z wyjątkiem węzłów chłonnych, których krótka oś musi mieć ≥15 mm) oraz która może zostać w powtarzalny sposób dokładnie zmierzona zgodnie z wytycznymi RECIST 1.1. Zmiany we wcześniej naświetlanej okolicy mogą być wykorzystane do określenia przebiegu choroby pod warunkiem, że wykazano progresję zmiany.
7.Pacjenci nie mogli być wcześniej poddani terapii immunologicznej, w tym m.in., otrzymywać przeciwciał anty-CTLA-4, anty -PD-1, anty -PD-L1 czy anty-PD-L2, ani terapeutycznych szczepionek przeciwnowotworowych.
8.Wydolna czynność narządów i szpiku kostnego
9.Dowody na stan po menopauzie lub ujemny wynik testu ciążowego wykonanego na próbce surowicy w przypadku pacjentek przed menopauzą

E.4

Principal exclusion criteria

1. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
2. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives
3. Receipt of last dose of an approved (marketed) anticancer therapy within 21 days prior to the first dose of study treatment.
4. Current or prior use of immunosuppressive medication within 14 days before the first dose of therapy.
5. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment.
6. History of active primary immunodeficiency
7. Known allergy or hypersensitivity to IP or any IP excipient

1.Równoczesne stosowanie jakiejkolwiek chemioterapii, leczenia jakimkolwiek IP, lekiem biologicznym lub lekami hormonalnymi z powodu choroby nowotworowej.
2.Przyjęcie przed podaniem pierwszej dawki badanego leczenia innej badanej terapii przeciwnowotworowej w okresie 28 dni lub 5 okresów półtrwania, w zależności od tego, co trwa dłużej.
3.Przyjęcie ostatniej dawki zarejestrowanej (dostępnej na rynku) terapii przeciwnowotworowej (chemioterapii, leczenia celowanego, terapii biologicznej, przeciwciał monoklonalnych itp.) w okresie 21 dni poprzedzających podanie pierwszej dawki leczenia badanego.
4.Aktualne lub wcześniejsze stosowanie leków immunosupresyjnych w okresie 14 dni poprzedzających pierwszą dawkę leczenia badanego
5.Aktywna lub udokumentowana wcześniej choroba autoimmunologiczna lub zapalna w okresie 3 lat poprzedzających rozpoczęcie leczenia.
6.Aktywny pierwotny niedobór immunologiczny w wywiadzie
7.Rozpoznana alergia lub nadwrażliwość na badany produkt lub jego składnik.

E.5 End points

E.5.1

Primary end point(s)

objective response rate

Odsetek odpowiedzi obiektywnych (ORR)

E.5.1.1

Timepoint(s) of evaluation of this end point

up to 3 years

do 3 lat

E.5.2

Secondary end point(s)

1. Duration of response
2. Disease control rate
3. Progression-free survival
4. Overall survival
5. Best objective response

1. czas trwania odpowiedzi (DoR)
2. wskaźnik kontroli choroby (DCR)
3. czas przeżycia wolnego od progresji (PFS)
4. przeżycie całkowite (OS)
5. najlepsza obiektywna odpowiedź (BoR)

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 3 years

do 3 lat

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

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

leczenie sekwencyjne

sequenced treatment

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

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

E.8.7

Trial has a data monitoring committee

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

Last visit of the last subject

„LVLS” (Last Visit Last Subject)

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

E.8.9.2

In all countries concerned by the trial days

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

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)

None

Nie dotyczy

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

2016-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-26

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
Orphan Designation Number:
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