Clinical Trials Register

Summary
EudraCT Number:	2011-000649-20
Sponsor's Protocol Code Number:	STAR-03
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:	2012-06-14
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

2011-000649-20

A.3

Full title of the trial

Phase II study of pre-operative treatment with external radiotherapy plus panitumumab in operable locally advanced rectal cancer (favourable and intermediate prognostic group) (RaP Study/STAR-03)

Studio di fase II sul trattamento pre-operatorio con radioterapia esterna e panitumumab in pazienti con tumore del retto in stadio localmente avanzato, operabile, a prognosi favorevole o intermedia

A.3.1

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

Phase II study of pre-operative treatment with external radiotherapy plus panitumumab in operable locally advanced rectal cancer (favourable and intermediate prognostic group) (RaP Study/STAR-03)

Studio di fase II sul trattamento pre-operatorio con radioterapia esterna e panitumumab in pazienti con tumore del retto in stadio localmente avanzato, operabile, a prognosi favorevole o intermedia (Studio RaP/STAR-03)

A.3.2

Name or abbreviated title of the trial where available

RaP/STAR-03 STUDY

STUDIO RaP/STAR-03

A.4.1

Sponsor's protocol code number

STAR-03

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 DELL'ISTITUTO TOSCANO 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	AMGEN Dompe' S.p.A
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	AOU CAREGGI
B.5.2	Functional name of contact point	Centro Coord.Sperim.Cliniche
B.5.3	Address:
B.5.3.1	Street Address	LARGO BRAMBILLA 3
B.5.3.2	Town/ city	FIRENZE
B.5.3.3	Post code	50134
B.5.3.4	Country	Italy
B.5.4	Telephone number	+39.055.794.5490
B.5.5	Fax number	+39.055.794.7553
B.5.6	E-mail	boni@aou-careggi.toscana.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	VECTIBIX*INFUS 1FL 20ML 20MG/M
D.2.1.1.2	Name of the Marketing Authorisation holder	AMGEN DOMPE' SpA
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	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	PANITUMUMAB
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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	anticorpo monoclonale umano del tipo IgG2

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

Operable locally advanced rectal cancer

Carcinoma del retto resecabile e localmente avanzato

E.1.1.1

Medical condition in easily understood language

Operable locally advanced rectal cancer

Carcinoma del retto operabile e in stadio localmente avanzato

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10038019
E.1.2	Term	Rectal adenocarcinoma
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 assess the complete pathological response rate after the pre-operative treatment with panitumumab in combination with external pelvic radiotherapy

Valutare il tasso di risposta patologica completa in seguito a trattamento pre-operatorio con panitumumab in combinazione con radioterapia esterna pelvica

E.2.2

Secondary objectives of the trial

To assess safety, pathological downstaging, R0 (surgical margin >1 mm/CRM-) resection rate, sphincter-saving surgery, time of disease free survival and overall survival, correlation between bio-markers and pathological responses

Valutare la sicurezza,il grado di riduzione dello stato di malattia,l’R0 (margine chirurgico >1 mm/CRM-),il tasso di resezione,la chirurgia con risparmio degli sfinteri,il tempo di sopravvivenza libera da malattia e la sopravvivenza globale,la correlazione tra bio-marcatori e le risposte patologiche

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Histologically diagnosis of adenocarcinoma of the mid-low rectum (within 12 cm from the anal verge); KRAS wild type; age ≥18 years; Karnofsky performance status of ≥70 at study entry; clinical stage T3 N- M0 or cT2-T3 N+ M0 - CRM; hemoglobin ≥ 9 g/dl; neutrophils ≥ 1.5 x 10^9/L; platelets ≥ 100 x 10^9/L; bilirubin level < 1.5 ULN; ASAT and ALAT <= 2.5 x ULN; serum creatinine < 1.5 x ULN; magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal; effective contraception for both, male and female patients if the risk of conception exists; signed and dated written informed consents

Diagnosi Istologica di adenocarcinoma del retto medio-basso (entro 12 cm dal margine anale); KRAS wild-type; Età≥ 18 anni; Karnofsky performance status ≥70 all'inizio dello studio; stadio clinico T3 N-M0 o CT2-T3 N + M0 - CRM; emoglobina ≥ 9 g / dl; neutrofili ≥1,5 x 10^9 / L; piastrine ≥ 100 x 10^9 / L; livello di bilirubina <1,5 ULN; ASAT e ALAT <= 2,5 x ULN; creatinina sierica < 1,5 x ULN; magnesio ≥ limite inferiore del normale; calcio ≥ limite inferiore del normale; contraccettivo efficace per entrambi, pazienti maschi e femmine se il rischio di concepimento esiste; consenso informato scritto firmato e datato.

E.4

Principal exclusion criteria

Prior radiotherapy or chemotherapy for rectal cancer; concurrent chronic systemic immune therapy; any investigational agent(s); previous exposure to EGF, monoclonal antibodies, signal transduction inhibitors or EGFR targeting therapy; clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months; known grade 3 or 4 allergic reaction to any of the components of the treatment; known drug abuse/ alcohol abuse; legal incapacity or limited legal capacity; medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed; women who are pregnant or breastfeeding consent; acute or subacute gastro-intestinal occlusion; any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial)

Precedente radioterapia o chemioterapia per il tumore del retto; concomitante terapia cronica del sistema immunitario; qualsiasi farmaco sperimentale; Precedente esposizione a FEG, anticorpi monoclonali, inibitori della trasduzione del segnale o EGFR targeting terapia; malattia coronarica clinicamente rilevante o storia di infarto del miocardio negli ultimi 12 mesi; reazioni allergiche di grado 3° o 4° note ad uno qualsiasi dei componenti del trattamento; abuso di droga / abuso di alcool noti; incapacità giuridica o capacità giuridica limitata; condizione medica o psicologica che, a parere del ricercatore, non permetterebbe al paziente di completare lo studio o firmare il consenso informato; donne in stato di gravidanza o che allattano; occlusione gastro-intestinale acuta o subacuta; presenza di altra malattia tumorale diversa da tumore cutaneo non-melanoma o carcinoma in situ della cervice (pazienti con una precedente neoplasia maligna, ma senza evidenza di malattia per ≥ 5 anni potranno essere arruolati nella sperimentazione)

E.5 End points

E.5.1

Primary end point(s)

Pathological Complete Response Rate (pCR)

Tasso di risposta patologica completa (pCR)

E.5.1.1

Timepoint(s) of evaluation of this end point

According to the therapeutic protocol timing, the surgery would be completed within 14 weeks from the patient's registration. Assuming that pathological results will be available 15 days later, the primary endpoint will me measured 16 weeks after the enrollment.

In accordo con la tempistica prevista dal protocollo terapeutico, l'intervento chirurgico dovrebbe essere eseguito entro 14 settimane dalla registrazione in studio. Considerando che il referto del patologo venga fornito nei 15 giorni successivi, si stima che il dato relativo all'endpoint primario sia disponibile entro 16 settimane dall'arruolamento.

E.5.2

Secondary end point(s)

Pathological downstaging rate, sphincter saving surgery rate, disease-free survival, R0 resection rate, time to relapse following surgery, overall survival time, incidence and severity of adverse events, significant laboratory changes, changes in vital signs, incidence of concomitant medications, changes from baseline over time in Karnofski performance status.

tasso di sottostadiazione della malattia, proporzione di chirurgie con risparmio degli sfinteri, tasso di resezione R0, durata della sopravvivenza libera da malattia, tempo di sopravvivenza complessiva, incidenza e gravità di eventi avversi, cambiamenti significativi di laboratorio, cambiamenti dei segni vitali, incidenza di farmaci concomitanti, cambiamenti rispetto al basale nel tempo del performance status Karnofski

E.5.2.1

Timepoint(s) of evaluation of this end point

The evaluation of secondary endpoints will be completed within 60 months from the enrollment

La rilevazione di tutti gli endpoint secondari sarà completata entro 60 mesi dall'arruolamento in studio

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

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

Yes

E.6.13.1

Other scope of the trial description

Pre-operative treatment activity, in terms of complete pathological response

Attività del trattamento pre-operatorio, in termini di tasso di risposte patologiche complete

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

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

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

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)

At the end of the follow wp period, patients will be followed according to standard clinical practice

Al termine del follow up previsto, i pazienti verranno seguiti secondo la normale pratica clinica

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

2012-06-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-05-15

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

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