Clinical Trials Register

Summary
EudraCT Number:	2015-005546-63
Sponsor's Protocol Code Number:	DOTATER1_26_15
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-28
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2015-005546-63

A.3

Full title of the trial

Peptide receptor radionuclide therapy in tumors with high expression of somatostatine receptors.

Terapia radiorecettoriale con analoghi marcati della somatostatina in tumori con elevata espressione dei recettori per la somatostatina.

A.3.1

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

Peptide receptor radionuclide therapy in tumors with high expression of somatostatine receptors.

Terapia radiorecettoriale con analoghi marcati della somatostatina in tumori con elevata espressione dei recettori per la somatostatina.

A.3.2

Name or abbreviated title of the trial where available

DOTATER1_26_15

A.4.1

Sponsor's protocol code number

DOTATER1_26_15

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	AZIENDA OSPEDALIERA ARCISPEDALE SANTA MARIA NUOVA/IRCCS DI REGGIO EMILIA
B.1.3.4	Country	Italy
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	A.O. di Reggio Emilia Arcispedale "S. Maria Nuova"
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	A.O. di Reggio Emilia Arcispedale S.Maria Nuova/IRCCS
B.5.2	Functional name of contact point	S.C. Medicina Nucleare
B.5.3	Address:
B.5.3.1	Street Address	Viale Risorgimento n. 80
B.5.3.2	Town/ city	Reggio Emilia
B.5.3.3	Post code	42123
B.5.3.4	Country	Italy
B.5.4	Telephone number	0522296313
B.5.5	Fax number	0522296153
B.5.6	E-mail	annibale.versari@asmn.re.it

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	177Lu-DOTA0-Tyr3-Octreotide
D.3.2	Product code	177Lu-DOTATOC
D.3.4	Pharmaceutical form	Radiopharmaceutical precursor
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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.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	90Y-DOTA0-Tyr3-Octrotide
D.3.2	Product code	90Y-DOTATOC
D.3.4	Pharmaceutical form	Radiopharmaceutical precursor
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Cancer patients with high expression of somatostatin receptors (neurendocrine tumors, thyroid tumors, lung tumors, meningiomas).

Pazienti con tumori esprimenti recettori della somatostatina.

E.1.1.1

Medical condition in easily understood language

Cancer patients with high expression of somatostatin receptors (neurendocrine tumors, thyroid tumors, lung tumors, meningiomas).

Pazienti con tumori esprimenti recettori della somatostatina.

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	10052399
E.1.2	Term	Neuroendocrine tumour
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 verify if there is a correlation between early response to therapy and 177Lu-SST-A uptake maximum percentage changes between basal evaluation and any other subsequent evaluation in target lesions in patients affected by NET.

Verificare se esiste una correlazione tra la risposta precoce alla terapia e la massima variazione percentuale di captazione del 177Lu-SST-A tra il basale e una qualunque successiva rilevazione nelle lesioni individuate come target in pazienti affetti da NET o da neoplasia con elevata espressione dei SSR.

E.2.2

Secondary objectives of the trial

To describe quantitatively the percentage change of 177Lu-SST-A uptake between basal evaluation and any other subsequent evaluation in target lesions in patients affected by NET.
b. To verify if there is a correlation between the onset of hematological and kidney toxicity, and the percentage change of 177Lu-SST-A uptake between baseline and any other subsequent evaluation in target lesions in patients affected by NET.
c. to verify if there are organ-specific differences in percentage change of 177Lu-SST-A uptake between baseline and any other subsequent evaluation in target lesions in patients affected by NET.
To evaluate OS, PFS and ORR at 3 and 12 months

Descrivere quantitativamente la variazione percentuale di captazione del 177Lu-SST-A tra la determinazione basale e ciascuna successiva rilevazione nelle lesioni individuate come target in pazienti affetti da NET o da neoplasia con elevata espressione dei SSR; verificare se esiste una correlazione tra l'insorgenza di tossicit¿, in particolare a livello renale ed ematologico, e la variazione percentuale di captazione del 177Lu-SST-A tra il basale e ciascuna successiva rilevazione nelle lesioni individuate come target in pazienti affetti da NET o da neoplasia con elevata espressione dei SSR; verificare se esistono differenze organo¿specifiche nelle variazione percentuale di captazione del 177Lu-SST-A tra il basale e ciascuna successiva rilevazione nelle lesioni individuate come target in pazienti affetti da NET o da neoplasia con elevata espressione dei SSR; valutare la quota di sopravviventi a 3 e 12 mesi dall¿inizio del trattamento,,l¿OS, la PFS e l¿ORR. (Overall Response Rate)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

patients older than 18
patients with neuroendocrine tumors or with high expression of somatostatin receptors tumors (at any anatomical site e.g. brain cancer, colorectal cancer, differentiated thyroid carcinoma, lymphoma, breast cancer, melanoma, lung cancer, renal cancer, sarcoma, prostate cancer, liver cancer, thymic neoplasms)
contrast Computed Tomography or Magnetic Resonance Imaging examination performed no longer than two months before the date of enrollment
68 Ga-SSA PET/CT examination performed no longer than two months before the date of enrollment and demonstrating the presence of lesions with high expression of somatostatin receptors
blood values within the estabilished ranges
ECOG performance status =2

Pazienti di età >18 anni e qualunque sesso o etnia
Diagnosi cito-istologica di NET, a qualsiasi sede, o di altro tumore SSTR-positivo, a qualsiasi sede (tumore cerebrale, tumore del colon-retto, carcinoma differenziato della tiroide, linfoma, tumore della mammella, melanoma, tumore del polmone, neoplasia renale, sarcoma, tumore della prostata, epatocarcinoma, neoplasie timiche)
Esame TC con mdc (preferibilmente) o RM (qualora la TC con mdc non sia effettuabile) eseguito entro i 2 mesi dalla data di arruolamento nel presente studio clinico
Presenza alla TC con mdc (o RM ) di almeno una lesione misurabile >1 cm
Esame 68Ga-SST-A PET/CT effettuato entro 2 mesi dalla data di arruolamento nel presente studio clinico in cui si dimostri elevata espressione dei recettori per la somatostatina in una o più lesioni. Si stabilisce di definire “elevata espressione dei recettori per la somatostatina” la dimostrazione all’esame 68Ga-SST-A PET/CT (analisi semi-quantitativa) di un rapporto di SUVmax tumore/SUVmean muscolo gluteo >4:1.
Adeguati valori ematochimici: globuli bianchi >2500/µL; piastrine >90000/µL; emoglobina >9 gr/dL; creatinina <2 mg/dL; bilirubina <2.5 mg/dL. L’inclusione di pazienti con iperbilirubinemie congenite verrà valutata caso per caso dal Proponente sulla base di criteri anamnestici e dei valori abituali di bilirubina
ECOG performance status =2

E.4

Principal exclusion criteria

pregnancy ( positive pregnancy test on serum)
refusal to stop breastfeeding
inadequate contraception
surgery, and/or chemotherapy, and/or radiation therapy (except for palliative radiation therapy) and /or biologics therapy performed in 4 four weeks before treatment
partecipation to other research protocols
bone marrow involvement >25%
life expectancy <6 months
inability to provide informed consent

Stato di gravidanza verificato mediante test di gravidanza (dosaggio della beta-HCG sul siero) il giorno della somministrazione
In caso di allattamento, rifiuto di sospendere l’allattamento
Non utilizzo di adeguati metodi contraccettivi (astensione dai rapporti sessuali nei 30 giorni precedenti la somministrazione, contraccettivi orali, contraccettivi di barriera, dispositivi intra-uterini, sterilizzazione)
Chirurgia, chemioterapia, radioterapia, terapia con farmaci biologici
Partecipazione ad altro protocollo clinico sperimentale terapeutico nelle 4 settimane precedenti la PRRT (eccetto il trattamento radioterapico con intento palliativo di lesioni sintomatiche in pazienti plurimetastatici)
Partecipazione ad altri studi che prevedano la somministrazione di farmaci sperimentali nelle 4 settimane precedenti il trattamento

E.5 End points

E.5.1

Primary end point(s)

Correlate early response to therapy and 177Lu-SST-A uptake maximum percentage changes between basal evaluation and any other subsequent evaluation in target lesions in patients affected by NET.

Correlare la risposta precoce alla terapia con la massima variazione percentuale di captazione del 177Lu-SST-A tra il basale e una qualunque successiva rilevazione nelle lesioni individuate come target in pazienti affetti da NET o da neoplasia con elevata espressione dei SSR.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 months

3 mesi

E.5.2

Secondary end point(s)

The percentage change of 177Lu-SST-A uptake between basal evaluation and any other subsequent evaluation in target lesions in patients affected by NET.; Correlation between the onset of hematological and kidney toxicity, and the percentage change of 177Lu-SST-A uptake.; Organ-specific differences in percentage change of 177Lu-SST-A uptake.; OS, THE PFS AND ORR

Entit¿ della variazione percentuale di captazione del 177Lu-SST-A tra la determinazione basale e ciascuna successiva rilevazione nelle lesioni individuate come target in pazienti affetti da NET o da neoplasia con elevata espressione dei SSR.; Relazione tra la variazione di captazione del 177Lu-SST-A e l¿insorgenza di tossicit¿ renale ed ematologica.; Differenze organo¿specifiche nelle variazione percentuale di captazione del 177Lu-SST-A.; La sopravvivenza, la PFS e l¿ORR

E.5.2.1

Timepoint(s) of evaluation of this end point

At third and subsequent cycle of therapy; 3 and 12 months; At third and subsequent cycle of therapy; 3 and 12 months

Dal terzo ai seguenti cicli di terapia; 3 e 12 mesi; Al terzo ciclo e successivi; 3 e 12 mesi

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

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)

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

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.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Information not present in EudraCT

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

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-01-28.

Yes

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

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

120

F.4.2.2

In the whole clinical trial

120

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)

-Active monitoring in cases of stable disease
-Drug therapy with somatostatin analogues, if not already in progress, as monotherapy or in combination with other molecular drugs target (Everolimus or sunitinib) in cases of progression disease.
-Chemotherapy (cisplatin, etoposide and ifosfamide - Pei scheme; temozolomide monotherapy or in combination with capecitabine; folfiri-irinotecan and fluorouracil; carboplatin and etoposide) in the mentioned cases;
- Locoregional therapies (chemoembolizatio

- sorveglianza attiva nei casi di malattia stabile
- in caso di progressione, adozione di terapia farmacologica con analoghi della
somatostatina, se non gi¿ in corso, in monoterapia o in associazione con altri farmaci a
bersaglio molecolare (es. Everolimus o sunitinib).
- Nei casi indicati, verr¿ valutata l¿ipotesi chemioterapica (cisplatino, etoposide e ifosfamide -
schema Pei ; temozolamide in monoterapia o in associazione a capecitabina; folfiri -
irinotecan e fluorouracile; carboplatino ed e

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

2016-05-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-17

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

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