Clinical Trials Register

Summary
EudraCT Number:	2016-003294-18
Sponsor's Protocol Code Number:	DOSEDENSE
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:	2021-06-08
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

2016-003294-18

A.3

Full title of the trial

Phase II Study of Neoadjuvant Chemotherapy With Dose-Dense Paclitaxel In Association With Carboplatin followed by Radical Surgery for Locally Advanced Cervical Cancer (FIGO stage IB2- IIIA) Patients.

Studio clinico di fase 2 a singolo braccio sulla chemioterapia dose dense nel trattamento neoadiuvante del carcinoma della cervice localmente avanzato .

A.3.1

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

Phase II Study of Neoadjuvant Chemotherapy With Dose-Dense Paclitaxel In Association With Carboplatin followed by Radical Surgery for Locally Advanced Cervical Cancer (FIGO stage IB2- IIIA) Patients.

Studio clinico di fase 2 a singolo braccio sulla chemioterapia dose dense nel trattamento neoadiuvante del carcinoma della cervice localmente avanzato .

A.3.2

Name or abbreviated title of the trial where available

DOSE DENSE

A.4.1

Sponsor's protocol code number

DOSEDENSE

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

A.5.4

Other Identifiers

Name:

DOSE DENSE

Number:

DOSE DENSE

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	FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
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	Fondazione IRCCS Istituto Nazionale Tumori
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	Fondazione IRCCS Istituto Nazionale Tumori
B.5.2	Functional name of contact point	S.C Oncologia Ginecologica
B.5.3	Address:
B.5.3.1	Street Address	Via G. Venezian 1
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20133
B.5.3.4	Country	Italy
B.5.4	Telephone number	02 23903697
B.5.5	Fax number	02 23903991
B.5.6	E-mail	domenica.lorusso@istitutotumori.mi.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 AHCL - 10 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DI VETRO DA 15 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ACCORD HEALTHCARE LIMITED
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 AHCL
D.3.2	Product code	Carboplatino AHCL
D.3.4	Pharmaceutical form	Solution for infusion
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	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	PACLITAXEL KABI - 6 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO VETRO DA 300 MG/50 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	FRESENIUS KABI ITALIA 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	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.3.11 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

Carcinoma della cervice uterina localmente avanzato

E.1.1.1

Medical condition in easily understood language

Uterin Cervical Cancer

Carcinoma della cervice uterina

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	10001197
E.1.2	Term	Adenocarcinoma of the cervix
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 evaluate the efficacy of the dose-dense administration of paclitaxel 80 mg/mq on days 1, 8 and 15 plus carboplatin (AUC5) on day 1 every 3 weeks in terms of clinical and pathologic responses

Valutare l¿attivita¿ del trattamento chemioterapico in termini di ottime risposte patologiche (risposta patologica completa+risposta parziale microscopica con infiltazione stromale <3 mm)

E.2.2

Secondary objectives of the trial

To evaluate the tolerability of the regimen in terms of toxicity according to CTCAE Version 4.0 criteria

To evaluate the Progression Free Survival (PFS) and Overall Survival (PFS) of the treated population

1. Valutare l¿attivita¿ del trattamento in termini di risposta clinica (completa, parziale, stabilizzazione di malattia) secondo i criteri Recist v 1.1
2. Valutare la sopravvivenza libera da progressione delle pazienti sottoposte al trattamento neoadiuvante
3. Valutare la sopravvivenza globale delle pazienti sottoposte al trattamento neoadiuvante
4. Valutare la tossicita¿ della chemioterapia neoadiuvante secondo i criteri CTCAE v4.03
5. Valutare la qualita¿ di vita delle pazienti sottoposte al trattamento chemioterapico dose dense

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histologic diagnosis of squamous cervical cancer or adenocarcinoma
• Clinical diagnosis of FIGO stage IB2-IIIA at gynecological examination
• ECOG Performance Status (ECOG PS): 0-1
• Age > 18 and < 75 years
• Life expectancy of at least 3 months
• Written informed consent
• Ability and willingness to comply with treatment and follow up assessments and procedures

1. Eta’ 18 - 75 years
2. Diagnosi istologica di carcinoma squamoso della cervice uterina e di adenocarcinoma
3. Stadio( valutazione clinica)
o Ib2
o IIa
o IIb
o IIIA

1. ECOG performance status < 1
2. Funzioni d’organo adeguate a ricevere una chemioterapia neoadiuvante:
- Ematopoietiche; Conta neutrofila= 1,500/mm^3; Piastrine = 100,000/mm^3; Emoglobina = 9 g/Dl
- Epatiche; AST e ALT = 1.5 volte il limite superiore della norma (ULN)* ; Fosfatasi Alcalina = 2.5 volte ULN* ; Bilirubina = 1.5 volte ULN NB: * = 3 volte ULN in caso di presenza di metastasi epatiche
- Renali; Creatinina Clearance = 45 ml/min o Creatininemia =1.5 x ULN
- Albuminemia >2.5 g/dl
- PT, PTT oINR>1.2 volte XULN
3. Consenso informato scritto
4. Aspettativa di vita>3 mesi
5. Abilita’ e volonta’ di partecipare a tutte le procedure indicate dallo studio

E.4

Principal exclusion criteria

• Previous or concomitant malignant neoplasia (not including basocellular or spinocellular skin carcinoma or in-situ carcinoma of the uterine cervix, provided they are being adequately treated)
• Serious heart disease, including heart failure, atrioventricular block of any degree, serious arrhythmia or history of one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease, coronary artery by-pass graft surgery, class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
• Hemoglobin < 9 g/dL, neutrophils < 1500/mm3, platelets < 100000/mm3
• Impairment of renal function: creatinine > 1.5 times the upper normal limit – UNL; calculated creatinine clearance < 50 mL/min; urine protein to creatinine ratio > 1: then, a 24-hour urine protein must be assessed and subject must have a 24-hour urine protein value <1gr to be eligible
• Impairment of liver function (SGOT or SGPT > 2.5 UNL, alkaline phosphatase > 2.5 ULN, total bilirubin > 1.5 times the UNL)
• Prothrombin time (PT) or international normalized ratio (INR) or activated partial thromboplastin time (PTT) > 1.2 times the UNL
• Pregnancy or breast feeding patients
• Any clinical conditions which can represent a contraindications to major surgery
• Localizations of disease not amenable for radical surgery
• Patients' inability to access the centre due to area of residence.

1. Pregressa neoplasia invasiva (con l’eccezione del basalioma cutaneo o del carcinoma cervicale in situ adeguatamente trattato)
2. Malattie cardiache serie (scompenso cardiaco di grado II-IV per NYHA, blocco atrioventricolare di qualsiasi grado, aritmia non controllata o storia nei precdenti 6 mesi di angioplastica o stenting coronario, infarto miocardico, angina instabile, malattia vascolare periferica sintomatica, by pass coronarico)
3. Gravidanza o allattamento
4. Ogni condizione clinica che rappresenta una controindicazione alla chirurgia maggiore
5. Sedi di malattia non asportabili chirurgicamente

E.5 End points

E.5.1

Primary end point(s)

To evaluate the efficacy of the dose-dense administration of paclitaxel 80 mg/mq on days 1, 8 and 15 plus carboplatin (AUC5) on day 1 every 3 weeks in terms of clinical and pathologic responses

Valutare l’attivita’ del trattamento chemioterapico in termini di ottime risposte patologiche (risposta patologica completa+risposta parziale microscopica con infiltazione stromale <3 mm)

E.5.1.1

Timepoint(s) of evaluation of this end point

2 years

2 anni

E.5.2

Secondary end point(s)

To evaluate the tolerability of the regimen in terms of toxicity according to CTCAE Version 4.0 criteria; To evaluate the Progression Free Survival (PFS) and Overall Survival (PFS) of the treated population

Valutazione della tollerabilit¿ del trattamento in termini di tossicit¿ secondo i criteri CTCAE Version 4.0.; Valutare la sopravvivenza libera da progressione e la sopravvivenza globale nelle pazienti sottoposte al trattamento

E.5.2.1

Timepoint(s) of evaluation of this end point

2 years; 2 years

2 anni; 2 anni

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

Yes

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)

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

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.8.5.1

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

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

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)

follow up

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

2016-10-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-09-22

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

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