Clinical Trials Register

Summary
EudraCT Number:	2005-000213-35
Sponsor's Protocol Code Number:	Palifermin20020402
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2006-11-29
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2005-000213-35

A.3

Full title of the trial

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the
Efficacy and Safety of Weekly Doses of Palifermin (Recombinant Human
Keratinocyte Growth Factor, rHuKGF) for the Reduction of Oral Mucositis in
Subjects With Advanced Head and Neck Cancer Receiving Radiotherapy With
Concurrent Chemotherapy (RT/CT).

Studio clinico di Fase 3, randomizzato, in doppio cieco, verso placebo, per valutare l’efficacia e la sicurezza di somministrazioni settimanali di Palifermin (Fattore di crescita per i cheratinociti ricombinante umano, rHuKGF) nella riduzione della mucosite orale in soggetti con neoplasia testa-collo (Head and Neck Cancer, HNC) in stadio avanzato che ricevono radioterapia e chemioterapia concomitante (RT/CT).

A.3.2

Name or abbreviated title of the trial where available

Palifermin 2002402

Palifermin 20020402

A.4.1

Sponsor's protocol code number

Palifermin20020402

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	AMGEN S.P.A.
B.1.3.4	Country	Italy
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Kepivance
D.2.1.1.2	Name of the Marketing Authorisation holder	AMGEN Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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.3.4	Pharmaceutical form	Powder for 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	palifermin
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	6.25
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	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	Yes
D.3.11.13.1	Other medicinal product type	Non Applicabile

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Mucositis associated with radiation therapy and
concurrent chemotherapy in subjects with HNC.

Mucosite associata a radioterapia e chemioterapia concomitante in soggetti con HNC.

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	14.0
E.1.2	Level	HLT
E.1.2	Classification code	10024530
E.1.2	Term	Lip and oral cavity neoplasms malignant
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 palifermin administered at the
dose of 180 µg/kg IV in 8 weekly doses relative to
placebo in reducing the incidence of severe [World
Health Organization Grade 3 or 4] oral mucositis (OM) in
subjects with locally advanced HNC receiving RT/CT as
definitive treatment for their disease.

Valutare l’efficacia di palifermin somministrato alla dose di 180 mg/kg EV in 8 somministrazioni settimanali, rispetto al placebo, nella riduzione dell’incidenza della mucosite orale (MO) severa [grado 3 o 4 WHO] in soggetti con HNC, localmente avanzato, sottoposti a RT/CT come terapia definitiva per la loro patologia.

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of palifermin at the
dose of 180 µg/kg IV in 8 weekly doses compared to
placebo during a 7-week course of RT/CT with cisplatin
(CDDP)
To evaluate the effect of palifermin on the clinical
sequelae of severe OM (eg, average patient-reported
mouth and throat soreness score), and on xerostomia
To evaluate long-term effects of palifermin on disease
outcome and survival after RT/CT.

Valutare la sicurezza e la tollerabilita' di palifermin somministrato alla dose di 180 mg/kg EV in ragione di 8 somministrazioni settimanali versus placebo durante un trattamento di 7 settimane di RT/CT con cisplatino (CDDP).Valutare l’effetto di palifermin sulle sequele cliniche della MO severa (ad esempio la media dei punteggi riportati dal paziente riguardo il dolore alla bocca e alla gola) e sulla xerostomia .Valutare gli effetti a lungo termine di palifermin sull’esito della malattia e sulla sopravvivenza dopo RT/CT.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Key Inclusion Criteria:
• Histologically documented squamous cell
carcinoma involving either the oral cavity,
oropharynx, nasopharynx, hypopharynx, or larynx
• Absence of second primary tumor confirmed by
triple endoscopy or by pharyngo/laryngoscopy
combined with imaging evidence (PET or CT
scan or MRI)
• Newly diagnosed, locally advanced stage HNC
(unresectable / unresected disease; American
Joint Committee on Cancer [AJCC] Stage III,
IVA, or IVB) amenable to RT/CT as the definitive
treatment modality
• Radiation treatment field to receive planned dose
of at least 50Gy to areas of the oral cavity /
oropharynx mucosa that can be visualized
(Subjects with larynx or hypopharynx tumors are
eligible only if the radiation oncologist anticipates
at least 2 of the 9 anatomical areas in the oral
cavity listed in Section 7.4 of this protocol
[Mucositis Assessments] will receive a total dose
of 50 Gy).
• Signed informed consent
• Subject is 18 years of age or older
• ECOG performance status (PS) ≤ 2
• Planned interval < 6 calendar days between
randomization and the first dose of RT
Baseline laboratory assessments:
- Hemoglobin (Hgb) ≥ 10g/dL
- White blood count (WBC) > 3.5 x 109/L or
- Absolute neutrophil count (ANC) > 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Serum bilirubin ≤ 1.5 x institutional upper limits
of normal (ULN)
- Serum creatinine ≤ 2.0 mg/dL; Subjects with a
serum creatinine ≥ 1.4 mg/dL and ≤ 2.0 mg/dL
need to demonstrate a 24-hr urinary creatinine
clearance ≥ 50 mL/min
- Serum or urine pregnancy test: Negative

Principali criteri di inclusione:
· Carcinoma squamocellulare documentato istologicamente che coinvolga la cavita' orale o l’orofaringe, la nasofaringe, l’ipofaringe o la laringe
· Assenza di un altro tumore primario confermata da tripla endoscopia o da faringo/laringoscopia combinata a diagnostica per immagini (PET o TAC o RM)
· Nuova diagnosi di HNC, localmente avanzato (non resecabile/non resecato chirurgicamente; Stadio III, IVA, o IVB secondo l’American Joint Committee on Cancer – AJCC) che possano essere sottoposti a RT/CT come modalita' definitiva di trattamento.
· Il campo di irradiazione deve comprendere aree di mucosa della cavita' orale/orofaringe che possano essere visualizzate e la dose dovra' essere di almeno 50 Gy.
(I soggetti con tumori alla laringe o ipofaringe sono eleggibili solamente se il radiologo oncologo prevede che almeno 2 delle 9 aree anatomiche nella cavita' orale elencati nella sezione 7.4 di questo protocollo [Mucositis Assessments] riceveranno una dose complessiva pari a 50 Gy).
· Firma del consenso informato
· Soggetto di eta' pari o maggiore di 18 anni
· ECOG (Eastern Cooperative Oncology Group) performance status (PS) £ 2
· Intervallo programmato < 6 giorni di calendario tra la randomizzazione e la prima somministrazione della RTParametri di laboratorio alla valutazione di “Baseline”:
- Emoglobina (Hgb) ³ 10g/dL- Conta dei globuli bianchi (WBC) > 3.5 x 109/L o Conta assoluta dei neutrofili (ANC) > 1.5 x 109/L
- Conta delle piastrine ³ 100 x 109/L
- Bilirubina sierica £ 1.5 x limite superiore del “Normal Range” dell’ istituzione
- Creatinina sierica £ 2.0 mg/dL; nei soggetti con creatinina sierica ³ 1.4 mg/dL e £ 2.0 mg/dL deve essere dimostrata una clearance della creatinina urinaria/24 ore ³ 50 mL/min
- Test di gravidanza su siero o urine con esito negativo

E.4

Principal exclusion criteria

Key Exclusion Criteria:
• Tumors of the lips, paranasal sinuses, salivary
glands, or of unknown primary
• Metastatic disease (M1) / Stage IV C
• Presence or history of any other primary
malignancy (other than curatively treated in situ
cervical cancer, or basal cell carcinoma of the
skin without evidence of disease for > 3 years)
• History of pancreatitis
• Plan to remove the tumor surgically before
completing the protocol RT / CT course
• Prior radiotherapy to the site of disease
• Prior chemotherapy
• Other investigational procedures
• Thirty days or less since receiving an
investigational product or device in another
clinical trial
. Current enrollment in another
clinical trial is not permitted unless the sole
purpose of the trial is for long-term followup/
survival data.
• Pregnant or breast-feeding women
• Refusal to use adequate contraceptive devices
during treatment phase
• Known sensitivity to any of the products
administered during dosing, including E coliderived
products
• Known to be sero-positive for human
immunodeficiency virus (HIV), hepatitis B virus
(HBV), or hepatitis C virus (HCV)
• Previous treatment on this study or with other
keratinocyte growth factors
and Administration
• Compromised ability of the subject to give written
informed consent and/or to comply with study
procedures
• Refusal to give written informed consent to
participate in this study and to sign the hospital
information release form
• Unwilling or unable to complete the patientreported
outcome questionnaires
• Psychological, social, familial, or geographical
reasons that would prevent regular follow-up.

Principali criteri di esclusione:
· Tumori delle labbra, dei seni paranasali, delle ghiandole salivari, o tumori primitivi latenti
· Malattia metastatica (M1) / stadio IV C
· Presenza o storia di altre neoplasie primarie (diversa da cancro cervicale trattato con intento curativo in situ o tumore a cellule basali della cute senza evidenza di malattia per > 3 anni)
· Storia di pancreatite
· Rimozione chirurgica pianificata del carcinoma prima del completamento del trattamento di RT/CT previsto dal protocollo
· Precedente radioterapia nel sito di malattia
· Precedente chemioterapia
· Altre procedure sperimentali
· Intervallo di 30 gg o meno dal trattamento con un prodotto o un dispositivo sperimentale in un altro trial clinico
. Non e' consentito il contemporaneo arruolamento in un’altra sperimentazione clinica a meno che l’unico scopo del trial sia l’acquisizione di dati di follow-up/sopravvivenza a lungo termine.
· Donne incinte o che allattano
· Rifiuto di ricorrere a idonei metodi di controllo delle nascite durante la fase di trattamento
· Sensibilita' nota a uno qualsiasi dei prodotti somministrati durante il dosaggio, compresi prodotti derivati dall’E. coli
· Nota sieropositivita' al virus dell’immunodeficienza umana (HIV), al virus dell’epatite B (HBV), o al virus dell’epatite C (HCV)
· Precedente trattamento in questo studio o con altri fattori di crescita per i cheratinociti
· Compromissione della capacita' del soggetto di dare il proprio consenso informato scritto e/o di conformarsi alle procedure di studio
· Rifiuto di dare il proprio consenso informato scritto alla partecipazione a questo studio
· Non intende o non e' in grado di compilare i questionari con le proprie valutazioni personali
· Motivi psicologici, sociali, familiari o geografici che potrebbero impedire un regolare follow-up.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint:
• Incidence (%) of severe oral mucositis (Grades 3
or 4 on the WHO oral mucositis scale)

Endpoint di efficacia primaria:
· Incidenza (%) di mucosite orale severa (Grado 3 o 4 sulla scala WHO della mucosite orale)

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

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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.8.6 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

Information not present in EudraCT

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

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	No
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	18
F.4.2	For a multinational trial
F.4.2.1	In the EEA	80
F.4.2.2	In the whole clinical trial	180

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

2006-06-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-05-22

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

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