Clinical Trials Register

Summary
EudraCT Number:	2011-001300-35
Sponsor's Protocol Code Number:	UCL11/0034
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:	2021-08-03
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-001300-35

A.3

Full title of the trial

A phase III multicentre trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with locally advanced cervical cancer

Studio internazionale randomizzato di fase III che confronta la chemioterapia settimanale di induzione seguita dalla chemio-radioterapia standard con la sola chemio-radioterapia standard nel trattamento di pazienti affette dal tumore della cervice uterina localmente avanzato

A.3.1

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

Clinical study, involving European and Extraeuropean clinical sites, which attributes treatment randomly to patients, and aims at comparing the efficacy of induction chemotherapy with weekly treatment followed by the standard chemoradiation vs. the efficacy of the treatment with the only standard chemoradiation, in patients with locally advanced cervical tumor.

Studio clinico che coinvolge più centri clinici europei ed extraeuropei, con assegnazione casuale al braccio di trattamento, che confronta l'efficacia della chemioterapia di induzione con trattamento settimanale seguita dalla chemio-radioterapia standard, con l'efficacia della sola chemio-radioterapia standard, nel trattamento di pazienti affette dal tumore della cervice uterina esteso

A.3.2

Name or abbreviated title of the trial where available

INTERLACE (INduction chemoThERapy in Locally Advanced CErvix )

A.4.1

Sponsor's protocol code number

UCL11/0034

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01566240

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	UNIVERSITY COLLEGE LONDON
B.1.3.4	Country	United Kingdom
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	University College of London
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”
B.5.2	Functional name of contact point	Laboratorio Metodologia della Ricer
B.5.3	Address:
B.5.3.1	Street Address	Via Privata Giuseppe La Masa, 19
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20156
B.5.3.4	Country	Italy
B.5.4	Telephone number	0239014519
B.5.5	Fax number	0233200231
B.5.6	E-mail	roldano.fossati@marionegri.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	Yes
D.2.1.1.1	Trade name	CARBOPLATINO TEVA - 1 FLACONE IV 5 ML 10 MG/ML
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA PHARMA B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Carboplatino
D.3.2	Product code	[n.a.]
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	CARBOPLATINO
D.3.9.1	CAS number	41575-94-4
D.3.9.2	Current sponsor code	n.a.
D.3.9.3	Other descriptive name	CARBOPLATIN
D.3.9.4	EV Substance Code	AS4
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	270
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	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: 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.2.1.1.1	Trade name	TAXOL - FLACONE 100 MG/16.7 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	BRISTOL MYERS SQUIBB S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.2	Product code	[n.a.]
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.3.9.2	Current sponsor code	n.a.
D.3.9.3	Other descriptive name	Paclitaxel, Taxol, Abraxane
D.3.9.4	EV Substance Code	AS5
D.3.10	Strength
D.3.10.1	Concentration unit	mg/m2 milligram(s)/square meter
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

locally advanced cervical cancer

tumore della cervice uterina localmente avanzato

E.1.1.1

Medical condition in easily understood language

locally advanced cervical tumor

tumore della cervice uterina localmente esteso

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

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	10028986
E.1.2	Term	Neoplasm cervix
E.1.2	System Organ Class	100000004864

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	10029103
E.1.2	Term	Neoplasm uterine cervix
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10028991
E.1.2	Term	Neoplasm cervix stage IV
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The main objective of the trial is to evaluate if the weekly induction chemotherapy followed by standard chemoradiation can be a concrete benefit in terms of overall survival in patients with locally advanced cervical cancer.

L'obbiettivo principale dello Studio è quello di valutare se la chemioterapia di induzione seguita dalla chemio-radioterapia standard possa essere di concreto beneficio in termini di sopravviveza globale per le pazienti affette dal tumore della cervice uterina localmente avanzato

E.2.2

Secondary objectives of the trial

The secondary objectives are:
-Progression free survival
-Adverse events
-Quality of life
-Patterns of relapse

Gli obiettivi secondari dello studio sono:
-Sopravvivenza libera dalla progressione (Progression free survival)
-Valutazione della safety dei trattamenti
-Qualità di vita
-Pattern di recidiva.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Principal Inclusion Criteria:
-Histologically confirmed FIGO stage Ib2- IVa squamous, adeno or adenosquamous carcinoma of the cervix (except those with disease extending to lower third of vagina). Patients with FIGO stage IB1 and positive lymph nodes are also eligible
-Deemed suitable and fit for radical chemoradiation
- Medically fit to receive carboplatin and paclitaxel
- ECOG performance status 0 – 1
- No evidence of active TB
- Aged 18 and over
- Adequate renal function, defined as a GFR = 60 ml/min calculated using the Wright equation (or = 50 ml/min for radioisotope GFR assessment)
- Adequate liver function, as defined by ALT or AST < 2.5 ULN and bilirubin < 1.25 ULN
- Adequate bone marrow function as defined by ANC =1.5 x 109/L, platelets = 100 x 109/L
- Using adequate contraception precautions if relevant
- A documented negative HIV test (patients recruited from high risk countries or who have moved within the past 10 years from high risk countries)
- A documented negative pregnancy test (if applicable)
- Capable of providing written or witnessed informed consent

Criteri di inclusione principali:
-Carcinoma della cervice uterine stadio FIGO IB2-IVA squamocellulare, adeno o adenosquamoso, istologicamente confermato tranne la malattia con estensione fino al terzo inferiore della vagina senza coinvolgimento della parete pelvica (FIGO III A). Anche le pazienti con stadio FIGO IB1 e con linfonodi positivi sono eleggibili per lo studio
-Giudizio di idoneità medica alla chemio-radioterapia radicale
-Giudizio di idoneità medica a ricevere carboplatino e paclitaxel
-HIV negatività (solo per i paesi con alto rischio o per i pazienti che si sono trasferiti negli ultimi 10 anni dai paesi ad alto rischio)
-Assenza di evidenza di tubercolosi attiva
-Stato generale ECOG 0-1
-Età=18 anni
-Funzionalità renale adeguata definita come GFR = 60ml/min secondo la formula di Wright o = 50ml/min se GFR determinata con utilizzo di radioisotopo
-Adeguata funzionalità epatica, definite da ALT o AST < di 2.5 limite superiore della norma, e livello di bilirubina < 1.25 del limite superiore della norma
-Adeguata funzione del midollo osseo definita da numero dei neutrofili assoluti = 1.5 x109/L, piastrine = 100 x 109/L
-Test di gravidanza negativo e documentato (se pertinente)
-Utilizzo di pratiche contraccettive adeguate (se pertinente)
-Consenso informato scritto

E.4

Principal exclusion criteria

Principal Exclusion Criteria:
- Previous pelvic malignancy (regardless of interval since diagnosis)
- Previous malignancy not affecting the pelvis (except basal cell carcinoma of the skin) where disease free interval is less than 10 years
- Positive lymph nodes (imaging or histological) above the aortic bifurcation
- Hydronephrosis which has not undergone ureteric stenting or nephrostomy except where the affected kidney is non-functioning
- Evidence of distant metastasis i.e. any non-nodal metastasis beyond the pelvis
- Previous pelvic radiotherapy
- Prior diagnosis of Crohn’s disease or Ulcerative colitis
- Uncontrolled cardiac disease (defined as cardiac function which would preclude hydration during cisplatin administration and any contraindication to paclitaxel)
- Pregnant or lactating

Criteri di esclusione principali:
-Pregressi tumori della pelvi (indipendentemente dall’intervallo trascorso)
-Pregressi tumori che non coinvolgono la pelvi (eccetto per il carcinoma basocellulare della cute), per i quali l’intervallo libero dalla malattia è inferiore a 10 anni
-Linfonodi positivi (radiologicamente o istologicamente) sopra la biforcazione aortica
-Idronefrosi non sottoposta a stent dell’uretere o nefrostomia, tranne situazioni in cui il rene affetto non è funzionante
-Evidenza di metastasi a distanza, cioè qualsiasi metastasi non linfonodale che abbia superato la pelvi
-Pregressa radioterapia della pelvi
-Pregressa diagnosi di malattia di Crohn o colite ulcerativa
-Malattia cardiaca non controllata (definita come patologia cardiaca che preclude l’idratazione durante la somministrazione di cisplatino e qualsiasi controindicazione al paclitaxel)
-Gravidanza ed allattamento

E.5 End points

E.5.1

Primary end point(s)

The primary end point is to evaluate Overall Survival

L'end point primario è valutare la sopravvivenza globale (OS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Overall Survival will be evaluated from the date of randomisation until the date of death from any cause

La sopravvivenza globale sarà valutata dalla data di randomizzazione fino alla data di morte per qualsiasi causa

E.5.2

Secondary end point(s)

Secondary end points are: -Progression free survival -Adverse events -Quality of life -Patterns of relapse

Gli end points secondari sono: - Sopravvivenza libera da progressione (Progression free survival) - Valutazione della safety dei trattamenti - Qualità di vita - Patterns di recidiva

E.5.2.1

Timepoint(s) of evaluation of this end point

Progression free survival will be evaluated from the date of randomisation until the date of first progression or death, whichever occurs first. Adverse events will be collected weekly during treatment, 4 weeks post treatment, 3 monthly for 2 years and 6 monthly for 3 years. Quality of life will be collected during treatment and at follow-up visits as outlined above. Patterns of relapse (local and/or systemic) will be assessed during follow-up from the date of randomisation until the date of first relapse.

La sopravvivenza libera da progressione sarà valutata dalla data di randomizzazione fino alla data della prima progressione o morte, a seconda di quale si verifica prima. Gli eventi avversi saranno raccolti ogni settimana durante il trattamento, 4 settimane dopo il trattamento, 3 mese per 2 anni e 6 mesi per 3 anni. Saranno raccolte durante il trattamento e durante le visite di follow-up, informazioni sulla Qualità di Vita come descritto sopra. I patterns di recidiva (locali e / o sistemici) verranno valutati durante il follow-up a partire dalla data di randomizzazione fino alla data della prima ricaduta

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

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)

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

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)

Yes

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

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

Mexico

South Africa

Ireland

Italy

United Kingdom

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

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

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

Patients affected by pathology under investigation who are not able to release their written Informed Consent ( the protocol doesn’t select for this kind of patients but allows their enrollment in presence of a legal representative)

Pazienti affette dalla patologia in Studio non in grado di fornire il proprio Consenso Informato scritto ( Il Protocollo non seleziona per tale tipologia di pazienti ma ne permette l’arruolamento in presenza di un rappresentate legale).

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

500

F.4.2.2

In the whole clinical trial

770

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)

Once follow-up programme is completed, patients will be followed up as per local clinical practice.

Una volta che il programma di follow-up sarà completato, le pazienti saranno seguite in accordo alla pratica clinica di ogni singolo centro.

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

2017-05-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-04-12

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