Clinical Trials Register

Summary
EudraCT Number:	2014-000857-35
Sponsor's Protocol Code Number:	UC-EGFR_INT01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-05-21
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

2014-000857-35

A.3

Full title of the trial

An open label, randomized, phase 2 study of Paclitaxel and Panitumumab compared to Paclitaxel alone in patients with relapsed or refractory urothelial cancer.

A.3.1

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

Anti EGFR therapy in relapsed/refractory urothelial carcinoma.

Terapia anti EGFR nel carcinoma della vescica metastatico ricaduto/refrattario.

A.3.2

Name or abbreviated title of the trial where available

Anti EGFR therapy in relapsed/refractory urothelial carcinoma.

Terapia anti EGFR nel carcinoma della vescica metastatico ricaduto/refrattario.

A.4.1

Sponsor's protocol code number

UC-EGFR_INT01

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	Azienda Farmaceutica: amgen
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 dei Tumori
B.5.2	Functional name of contact point	Trial center
B.5.3	Address:
B.5.3.1	Street Address	Via 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	02-23903824
B.5.5	Fax number	02-23903991
B.5.6	E-mail	trialcenter@istitutotumori.mi.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role
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	VECTIBIX - 20 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO 1 FLACONCINO (VETRO) 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	AMGEN EUROPE 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.3.4	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	PANITUMUMAB
D.3.9.1	CAS number	339177-26-3
D.3.9.2	Current sponsor code	Vectibix
D.3.9.3	Other descriptive name	PANITUMUMAB
D.3.9.4	EV Substance Code	SUB25390
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
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	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 - 6MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DA 150 MG
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	L01CD01
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.3.11 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	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

relapsed/refractory Metastatic urothelial carcinoma

Carcinoma uroteliale metastatico ricaduto/refrattario

E.1.1.1

Medical condition in easily understood language

advanced baldder cancer

carcinoma della vescica in fase avanzata

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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10064467
E.1.2	Term	Urothelial carcinoma
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

progression free survival

Sopravvievenza libera da progressione

E.2.2

Secondary objectives of the trial

overall survival, toxicity, safety

sopravvivenza globale, tossicità, sicurezza

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Histologically confirmed diagnosis of transitional cell tumors of the bladder or the urothelium. Presence of divergent histologies (i.e. squamous-cell tumor, adenocarcinoma, small cell carcinoma, micropapillary variant) may be acceptable provided that there is prevalence (> 50%) of urothelial component.
• Locally advanced or metastatic disease.
• Age ≥18 and ≤75.
• Measurable disease criteria, defined as ≥1 unidimensionally measurable lesion ≥2 cm by conventional techniques or ≥1 cm by spiral CT scan.
• Failure (i.e. disease relapse/progression by RECIST v1.1 criteria) of one or two platinum-based (either cisplatin or carboplatin) conventional chemotherapy regimen for metastatic disease (second and third-line setting will be the objective of this study).
• Neoadjuvant/adjuvant therapy will be counted as one prior chemotherapy line if relapse has occurred within 6 months of the last cycle of chemotherapy.
• Female subject is either:
o post-menopausal for at least one year before the screening visit, or
o surgically sterilized, or
o willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 2 months following the last dose of panitumumab.
• Male subject, even if surgically sterilized (ie, status postvasectomy), agrees to use an acceptable method for contraception during the entire study treatment period through 2 months after the last dose of panitumumab.
• Absolute neutrophil count (ANC) >1,500/mm³, platelets >100,000/mm³, Hgb >9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines.
• Total bilirubin ≤1.5 x upper limit of nomal (ULN), SGOT (AST) and SGPT (ALT)< 2.5 x ULN. AST and/or ALT may be up to 5X ULN if with known liver mets.
• Adequate renal function as defined by: Calculated creatinine clearance must be ≥30 mL/minute.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 & life expectancy of at least 12 weeks.
• Patients must be accessible for treatment and follow up as well as they must be willing and capable to comply with the requirements of the study.

• Consenso informato scritto.
• Età ≥ 18 anni.
• Diagnosi istologicamente confermata di carcinoma a cellule transizionali della vescica o delle vie urinarie.
• Positività per espressione immunoistochimica di EGFR con uno score di 2+ o 3+.
• Malattia localmente avanzata/metastatica.
• Ricaduta/progressione dopo 1 o 2 linee di trattamento chemioterapico platino (cis- o carboplatino) contenente per malattia metastatica.
• La ricaduta/progressione entro 12 mesi da un precedente trattamento peri-operatorio platino-contenente sarà considerata come una linea di chemioterapia precedente.
• Malattia misurabile, definita come la presenza di ≥ 1 lesione misurabile uni-dimensionalmente con metodiche convenzionali (TC) di ≥ 2 cm o di ≥ 1 cm se misurata con TC spirale.
• Adeguata funzione midollare, epatica e renale in accordo ai valori riportati nel full protocol.
• ECOG performance status di 0-2.
• Soggetti che accettino di praticare un’effettiva contraccezione durante l’intera durata dello studio, a meno che esista documentazione di infertilità (un test di gravidanza negativo eseguito entro le 2 settimane precedenti l’inizio dello studio è necessario per tutte le donne in età fertile).
• Aspettativa di vita di almeno 12 settimane.
• Possibilità e disponibilità a seguire le procedure previste dal protocollo.

E.4

Principal exclusion criteria

• Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
• Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
• Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed.
• Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Presence of interstitial pneumonitis, pulmonary fibrosis, evidence of interstitial pneumonitis, or pulmonary fibrosis.
• Female subject who is either pregnant or breast-feeding or planning to become pregnant during treatment and within 2 months of the last dose of panitumumab. Confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin (-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion. For guidance in defining active infection for hepatitis B, please refer to the WHO guidelines. (World Health Organization, Global Alert and Response (GAR), Hepatitis B. who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/index4.html)
• Prior administration of an anti EGFR-targeted agent, including but not limited to panitumumab.
• Administration of myeloid growth factors or platelet transfusion within 14 days prior to the first dose of study treatment.
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.

• Importanti patologie cardiovascolari nei 6 mesi che precedono l’inizio di Panitumumab e/o Taxolo, quali:
o Infarto miocardico (IM), angina instabile (l’IM a più di 6 mesi dall’ingresso nello studio è ammesso), scompenso cardiaco di grado ≥ 2 secondo i criteri NYHA, aritmie di qualsiasi natura che richiedano l’uso di farmaci (beta-bloccanti o digossina sono permessi), ipertensione (PA media > 140/90 mm/Hg) non controllata, prolungamento dell’intervallo QT (QTc) > 450 msec.
o Storia di infarti cerebro-vascolari, embolia polmonare o trombosi venosa profonda non trattata entro i 6 mesi che precedono l’inizio del protocollo.
• Infezione da HIV o epatite cronica attiva di tipo B e C.
• Infezioni clinicamente serie in fase attiva (di grado > 2 dei CTCAE v.4.03).
• Metastasi cerebrali o meningee sintomatiche (a meno di un tempo > 6 mesi da un precedente trattamento curative e malattia clinicamente stabile al momento dell’ingresso nello studio).
• Anamnesi positiva per crisi epilettiche che richiedono specifico trattamento medico (come cortico-steroidi e anti-epilettici).
• Impossibilità ad assumere farmaci orali e/o gravi co-morbidità che pregiudicano il corretto assorbimento del farmaco sperimentale.
• Evidenza o anamnesi positiva per diatesi emorragica.
• Dialisi renale.
• Seconda neoplasia pregressa o concomitante fatta eccezione per il carcinoma in situ della cervice, il carcinoma basocellulare o qualsiasi altra neoplasia trattata in modo radicale ad un tempo > 5 anni rispetto alla data di ingresso nello studio.
• Gravidanza e allattamento.
• Presenza di infezione non controllata.
• Chirurgia maggiore o trauma grave nei 28 giorni precedenti alla prima dose di Panitumumab e/o presenza di ferite aperte, fratture o ulcere.
• Ogni tossicità pre-esistente correlata al precedente trattamento chemioterapico di grado > 1 e/o ingravescente.
• Nota ipersensibilità a farmaci chimicamente correlabili ad Panitumumab.
• Presenza di qualsiasi condizione medica, disfunzione metabolica o psichiatrica che possa limitare la piena osservanza delle procedure dello studio o aumentare il rischio associato all’assunzione del farmaco.

E.5 End points

E.5.1

Primary end point(s)

Progression free survival

E.5.1.1

Timepoint(s) of evaluation of this end point

2 months

2 mesi

E.5.2

Secondary end point(s)

overall survival. safety, toxicity

E.5.2.1

Timepoint(s) of evaluation of this end point

2 months

2 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

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

Yes

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.8.6 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

4 months of follow up of the last enrolled subject

quattro mesi di follow up dell'ultimo soggetto arruolato

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

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)

tac evaluation every 2 months

rivalutazione TAC ogni 2 mesi

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

2015-03-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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IMP with orphan designation in the indication
Orphan Designation Number:
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