Clinical Trials Register

Summary
EudraCT Number:	2020-006068-99
Sponsor's Protocol Code Number:	DuoNen2020
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:	2021-01-27
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2020-006068-99

A.3

Full title of the trial

Tandem therapy LutaPol/ItraPol (177Lu / 90Y-DOTATATE) as an effective method in the treatment of neuroendocrine neoplasms, Acronym: DuoNen, 2019 / ABM / 01/00077

Zastosowanie terapii tandemowej LutaPol/ItraPol (177Lu/90Y-DOTATATE) jako skutecznego narzędzia w leczeniu nowotworów neuroendokrynnych, Akronim: DuoNen, 2019/ABM/01/00077

A.3.1

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

Application of radioisotope therapy as an effective method in the treatment
of neuroendocrine neoplasms

Zastosowanie terapii radioizotopowej jako skutecznego narzędzia w leczeniu nowotworów neuroendokrynnych

A.3.2

Name or abbreviated title of the trial where available

DuoNen

A.4.1

Sponsor's protocol code number

DuoNen2020

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	Narodowe Centrum Badań Jądrowych, Ośrodek Radioizotopów POLATOM
B.1.3.4	Country	Poland
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Agencja Badań Medycznych
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Narodowe Centrum Badań Jądrowych, Ośrodek Radioizotopów POLATOM
B.5.2	Functional name of contact point	Project Leader, dr R. Mikołajczak
B.5.3	Address:
B.5.3.1	Street Address	ul. Andrzeja Sołtana 7
B.5.3.2	Town/ city	Otwock
B.5.3.3	Post code	05-400
B.5.3.4	Country	Poland
B.5.4	Telephone number	0048222731702
B.5.5	Fax number	004822 7180350
B.5.6	E-mail	Renata.Mikolajczak@polatom.pl

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	DuoNEN
D.3.2	Product code	DOTA-TATE, [177Lu]Lu-DOTA-TATE, [90Y]Y-DOTA-TATE
D.3.4	Pharmaceutical form	Solution for injection
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	DOTA-TATE
D.3.9.1	CAS number	177943-89-4
D.3.9.2	Current sponsor code	DOTA-TATE
D.3.9.3	Other descriptive name	DOTATATE
D.3.9.4	EV Substance Code	SUB181362
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LUTETIUM (177LU) OXODOTREOTIDE
D.3.9.2	Current sponsor code	177Lu]Lu-DOTA-TATE
D.3.9.3	Other descriptive name	Lutetium (177Lu) oxodotreotide
D.3.9.4	EV Substance Code	SUB180110
D.3.10	Strength
D.3.10.1	Concentration unit	GBq/ml gigabecquerel/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	[90Y]Y-DOTA-TATE
D.3.9.3	Other descriptive name	YTTRIUM OXODOTREOTIDE Y-90
D.3.9.4	EV Substance Code	SUB130381
D.3.10	Strength
D.3.10.1	Concentration unit	GBq/ml gigabecquerel/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diagnosed and confirmed histopathologically disseminated or locally unresectable, well and moderately differentiated (G1 and G2) neuroendocrine neoplasms of the gastrointestinal tract (GEP-NET)

Rozpoznany i potwierdzony histopatologicznie rozsiany lub miejscowo nieresekcyjny, dobrze i średniozróżnicowany (G1 i G2) nowotwór neuroendokrynny przewodu pokarmowego (GEP-NET).

E.1.1.1

Medical condition in easily understood language

Disseminated or locally unresectable, well and moderately differentiated neuroendocrine neoplasm of the gastrointestinal tract

Rozsiany lub miejscowo nieresekcyjny, dobrze i średniozróżnicowany nowotwór neuroendokrynny przewodu pokarmowego.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim of the study is to develop an algorithm for the treatment of GEP-NET patients using ItraPol and LutaPol isotope mixtures (177Lu-DOTATATE and 90Y-DOTATATE) based on personalized dosimetry.

Celem badania jest opracowanie algorytmu leczenia chorych na GEP-NET z użyciem mieszanek izotopowych ItraPol i LutaPol (177Lu-DOTATATE i 90Y-DOTATATE) na podstawie spersonalizowanej dozymetrii.

E.2.2

Secondary objectives of the trial

The specific goal is to assess the effectiveness and safety of personalized treatment of GEP-NET patients using 177Lu-DOTATATE and 90Y-Lu-DOTATATE mixtures compared to standard treatment of NEN patients using 177Lu-DOTATATE

Ocena skuteczności i bezpieczeństwa spersonalizowanego leczenia chorych na GEP-NET z użyciem mieszanek 177Lu-DOTATATE i 90Y -DOTATATE w porównaniu do standardowego leczenia u tych chorych z użyciem 177Lu-DOTATATE.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

I. Related to the neuroendocrine tumor
a) advanced, unresectable, confirmed in histopathological test, well and moderately differentiated (G1 and G2) neuroendocrine neoplasms, in which high expression of somatostatin receptors have been confirmed by Somatostatin Receptor Imaging (SRI) in PET/CT using 68Ga-DOTA-TATE, which has been performed not earlier than 12 weeks prior to qualification.
b) disease progression according to RECIST 1.1 criteria diagnosed in multiphase CT or dynamic MRI within 18 months, given the qualification investigation is performed not earlier than 12 weeks prior to qualification.
c) Laboratory test:
◦ morphology with smear Hb > 9g/dl, platelets > 100 tys./μl, leukocytes > 3 k/μl, neutrocytes > 1,5 k/μl,
◦ creatinine <120 μmol/l (1,36 mg/dl), eGFR>45 ml/min.
◦ AlAT, AspAT, total bilirubin (values not higher than 3x reference standard)
II. Related to the patient
Overall status of the patient in Karnofsky’s scale ≥60%. Expected life span over 6 months. Age over 18 years, no age limit in adults. Ability to express informed consent to take part in the trial.

I. Związane z nowotworem neuroendokrynnym:
a) Obecność zaawansowanego, nieresekcyjnego, potwierdzonego w badaniu histopatologicznym dobrze i średniozróżnicowanego (G1 i G2) nowotworu neuroendokrynnego, z wysoką ekspresją receptorów somatostatynowych w badaniu obrazowania receptorów somatostatynowych (SRI) w technice PET/CT z użyciem 68Ga-DOTA-TATE wykonanym nie wcześniej niż 12 tygodni przed kwalifikacją
b) Stwierdzenia progresji choroby nowotworowej wg kryteriów RECIST 1.1 w wielofazowym badaniu TK lub dynamicznym MR w ciągu 18 miesięcy, przy czym badanie kwalifikujące nie może być wykonane wcześniej niż 12 tygodni przed kwalifikacją
c) Badania laboratoryjne:
◦ morfologia krwi z rozmazem Hb > 9g/dl, płytki krwi > 100 tys./μl, leukocyty > 3 tys./μl, neutrocyty > 1,5 tys./μl,
◦ kreatynina <120 μmol/l (1,36 mg/dl), eGFR>45 ml/min.
◦ AlAT, AspAT, bilirubina całkowita (wartości nieprzekraczające 3x normy referencyjnej)
II. Związane z pacjentem:
Ogólny stan Pacjenta w skali Karnofsky’ego ≥60% (p. Dodatek 1).Spodziewany okres przeżycia powyżej 6 miesięcy
Wiek powyżej 18 roku życia, bez górnej granicy wieku.
Zdolność do wyrażenia świadomej zgody na udział w badaniu. Podpisanie formularza świadomej zgody na udział w badaniu

E.4

Principal exclusion criteria

I. Related to the neuroendocrine tumor
Disability of the patient (Karnofsky <60)
Expected life span below 6 months
Anther malignant neoplastic disease treatment within 5 years prior to randomization
Related to current therapies and medical interventions or those in the past
Earlier PRRT
Chemotherapy or molecular therapy (due to NEN or another neoplasm) in the past
II. Related to the patient
Age less than 18 years
Pregnancy or breast feeding
Patients with urinary flow disorders or with non-treated urinary incontinence without catheter protection.
Disability to express informed consent to take part in the trial.
Unsigned informed consent form for taking part in the trial.

I. Związane chorobą nowotworową:
Niesprawność pacjenta (Karnofsky <60)
Spodziewany okres przeżycia poniżej 6 miesięcy.
Leczenie innego nowotworu złośliwego w okresie krótszym niż 5 lat przed randomizacją
Związane z terapiami i ingerencjami medycznymi stosowanymi obecnie i w przeszłości:
PRRT w przeszłości.
Chemioterapia lub leczenie malekularne (z powodu NEN lub innego nowotworu) w przeszłości.
II. Związane z pacjentem:
Wiek poniżej 18 roku życia.
Ciąża lub karmienie piersią.
Pacjenci z zaburzeniami odpływu moczu z pęcherza moczowego albo z nieleczonym nietrzymaniem moczu bez zabezpieczenia cewnikiem.
Brak zdolności do wyrażenia świadomej zgody na udział w badaniu.
Niepodpisanie formularza świadomej zgody na udział w badaniu.

E.5 End points

E.5.1

Primary end point(s)

Disease progression assessed by CT or MRI according to RECIST 1.1

Progresja choroby nowotworowej oceniania w badaniu TK lub MR w skali RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoints of Primary End Point evaluation:
control imaging investigations (CT or MRI) using the technique identical with the one based on which the patient was qualified for the trial, performed after 3,6,12,24,36,49,60 months after completion of therapy with assessment according to RECIST 1.1

Momenty ewaluacji Pierwszorzędowego Punktu Końcowego:
kontrolne badania obrazowe (TK lub MR) techniką identyczną z techniką na podstawie której pacjent został zakwalifikowany do leczenia po 3, 6, 12, 24, 36, 48, 60 miesiącach od zakończonej terapii z oceną wg RECIST 1.1.

E.5.2

Secondary end point(s)

Assessment of effectiveness and safety of personalized therapy

Ocena skuteczności i bezpieczeństwa spersonalizowanego leczenia.

E.5.2.1

Timepoint(s) of evaluation of this end point

It is planned to perform biochemical tests during visit W1, during hospitalization and in the course of observation every 3 months (tests of blood morphology, urea, creatinine, eGFR, bilirubin). Total volume of blood collected at single timepoint - 6.8 ml.

Planowane jest wykonanie badań biochemicznych podczas wizyty W1, w trakcie hospitalizacji oraz w trakcie okresu obserwacji co 3 miesiąc (na oznaczenie morfologii, mocznika, kreatyniny, eGFR, ALT, bilirubiny). Łączna ilość krwi w trakcie jednego pobrania - 6,8 ml.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

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)

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

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

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

Yes

E.8.2.3.1

Comparator description

177Lu-DOTATATE dawkami o stałej radioaktywności 7400 MBq

177Lu-DOTATATE with doses of constant radioactivity of 7,400 MBq

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

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

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

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

2021-09-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-20

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials