Clinical Trials Register

Summary
EudraCT Number:	2013-005596-40
Sponsor's Protocol Code Number:	SFT-AX2014
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:	2014-01-20
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

2013-005596-40

A.3

Full title of the trial

Phase II Study of Axitinib in Advanced Solitary Fibrous Tumor

Studio di fase 2 su Axitinib nel tumore solitario fibroso avanzato

A.3.1

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

Phase II Study of Axitinib in Advanced Solitary Fibrous Tumor

Studio di fase 2 su Axitinib nel tumore solitario fibroso avanzato

A.4.1

Sponsor's protocol code number

SFT-AX2014

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00828919

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	Pfizer italy S.r.l.
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	Clinical Trial Office
B.5.3	Address:
B.5.3.1	Street Address	Via G. Venezian 1
B.5.3.2	Town/ city	Milan
B.5.3.3	Post code	20133
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390223903287
B.5.5	Fax number	+390223903353
B.5.6	E-mail	federica.favales@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	Inlyta
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer 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	Axitinib
D.3.2	Product code	AG-013736
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral 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

Advanced solitary fibrous tumor

Tumore solitario fibroso avanzato

E.1.1.1

Medical condition in easily understood language

Advanced solitary fibrous tumor

Tumore solitario fibroso 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	16.1
E.1.2	Level	HLT
E.1.2	Classification code	10041298
E.1.2	Term	Soft tissue sarcomas histology unspecified
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Overall tumor Response Rate, according to Choi

Risposta tumorale globale secondo i criteri CHOI

E.2.2

Secondary objectives of the trial

RECIST response rate
Overall Survival
Progression Free Survival
Clinical Benefit
Post-treatment Axitinib target status assessment

Risposta tumorale secondi i criteri RECIST
Tasso di sopravvivenza globale
Progressione libera da malattia (PFS)
Beneficio clinico
Status target di Axitinib (VEGFR e PDGFR) dopo trattamento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histological centrally confirmed diagnosis of solitary fibrous tumor

• Expression of PDGFRB and/or VEGFR2 by immunohistochemistry on formalin fixed-paraffin embedded (FFPE) material as minimal requirement. Activation of PDGFRB and/or VEGFR2 by real time PCR of PDGFB and VEGFA on FFPE material (if in sufficient quantity) or by biochemistry on frozen material (if available).

• Locally advanced disease (i.e. surgical resection of local disease unfeasible radically, or unaccepted by the patient, or amenable to become less demolitive, or feasible, or easier, after cytoreduction) and/or metastatic disease

• Measurable or evaluable disease

• Evidence of progression by RECIST during the 6 months before study entry

• 1st-line vs 3-rd-line

• Eastern Cooperative Oncology Group (ECOG) Performance Status = 0, 1, 2

• Adequate bone marrow function, defined as the following: ANC >1.5 x 109/L, platelets >100 x 109/L, Hb >9 g/dL. Blood transfusions are allowed to reach the baseline requested Hb level

• Adequate organ function, defined as the following: total bilirubin within normal institutional limits (but in case of Gilbert’s syndrome), AST (SGOT) and ALT (SGPT) <2.5 x UNL, creatinine <1.5 x ULN. within normal institutional limits or creatinine clearance  60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

• Cardiac ejection fraction ≥50% as measured by echocardiogram

• Age > 18 yrs

• Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study and for up to 3 months following discontinuation of study drug.

• No history of arterial and/or venous thromboembolic event within the previous 12 months.

• Written, voluntary informed consent

- Conferma istologica di tumore fibroso solitario
- Espressione di PDGFRB e / o VEGFR2 mediante immunoistochimica su materiale paraffinato fissato in formalina (FFPE) come requisito minimo. Attivazione di PDGFRB e / o VEGFR2 mediante real time PCR di PDGFB e VEGFA su materiale FFPE (se in quantità sufficiente) o biochimica su materiale congelato (se disponibili).
- Malattia localmente avanzata e/o malattia metastatica
- Malattia misurabile
- Progressione secondo RECIST entro i 6 mesi precedenti all’ingresso nello studio
- Prima linea versus terza linea
- ECOG PS 0,1,o 2
- Funzionalità midollare adeguata, definita come la seguente: ANC> 1,5 x 109 / L, piastrine> 100 x 109 / L, Hb> 9 g / dL. Le trasfusioni di sangue sono autorizzati a raggiungere il livello basale di emoglobina richiesto.
- Funzionalità organica adeguata, definita come la seguente: bilirubina totale entro i limiti istituzionali normali (tranne in caso di sindrome di Gilbert), AST (SGOT) e ALT (SGPT) <2,5 x UNL, creatinina <1,5 x ULN. entro limiti normali istituzionali o di clearance della creatinina > 60 mL/min/1.73 m2 per i pazienti con livelli di creatinina sopra la norma istituzionale
- Frazione di eiezione > 50% misurata tramite ecocardiogramma
- Età >di 18 anni
- Pazienti di sesso femminile in età fertile devono avere un test di gravidanza negativo entro 7 giorni prima dell'inizio dell’assunzione del farmaco in studio. Le donne in post-menopausa devono essere in amenorrea da almeno 12 mesi per essere considerate potenzialmente non fertili. Pazienti di sesso maschile e femminile potenzialmente fertili devono accettare di impiegare un efficace metodo di controllo delle nascite per tutta la durata dello studio e per un massimo di tre mesi dopo l'interruzione del farmaco in studio.
- Nessuna storia di eventi tromboembolici arteriosi e/o venosi nei 12 mesi precedenti.
- Firma del consenso informato

E.4

Principal exclusion criteria

• Other primary malignancy with <5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse

• Previous treatment with any other investigational or not investigational agents and or radiation therapy within 28 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Major surgery within 2 weeks prior to study entry

• Previous radiotherapy to 25 % of the bone marrow

• Concomitant other investigational agents or concurrent anticancer therapy. In addition, all herbal (alternative) medicines are excluded

• Grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e., history of uncontrolled or symptomatic angina, history of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation, myocardial infarction < 6 months from study entry, uncontrolled or symptomatic congestive heart failure, ejection fraction below the institutional normal limit)

• Known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)

• Known diagnosis of human immunodeficiency virus (HIV) infection

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Axitinib

• Expected non-compliance to medical regimens

- Anamnesi di altre neoplasie (ad eccezione del basalioma o del carcinoma in situ della cervice, adeguatamente trattati), a meno che non siano in remissione da più di 5 anni o altre neoplasie con scarso potenziale di recidiva
- Precedente trattamento con altri farmaci sperimentali o non sperimentali e o radioterapia entro 28 giorni dalla prima giornata di trattamento con il farmaco in studio farmaco, o pazienti che non sono guariti da eventi avversi dovuti ad agenti somministrati più di 4 settimane prima
- Chirurgia maggiore nelle 2 settimane precedenti l'ingresso nello studio
- Trattamento radiante precedente al 25% o più del midollo osseo
- Altri agenti sperimentali concomitanti o terapia antitumorale concomitante. Inoltre, sono esclusi tutte le erbe medicinali (alternative).
- Problemi cardiaci di grado III / IV come definiti dalla New York Heart Association (cioè, storia di angina incontrollata o sintomatica, storia di aritmie che richiedono farmaci, o clinicamente significativa, ad eccezione della fibrillazione atriale asintomatica che richiede anticoagulante, infarto del miocardio <6 mesi a decorrere dall'entrata studio, insufficienza cardiaca congestizia non controllata o sintomatica, frazione di eiezione inferiore al limite istituzionale normale)
- Patologie epatiche croniche (ad esempio, epatite cronica attiva e cirrosi con l'eccezione dei pazienti con sindrome di Gilbert, calcoli biliari asintomatici, metastasi epatiche o malattia epatica stabile cronica a giudizio del ricercatore)
- Diagnosi nota di infezione da HIV
- Storia di reazioni allergiche attribuibili a composti chimici simili a quelli utilizzati per la composizione biologica di Axitinib
- Attesa non compliance allo studio clinico

E.5 End points

E.5.1

Primary end point(s)

Overall tumor Response Rate, according to Choi

Risposta tumorale globale secondo i criteri CHOI

E.5.1.1

Timepoint(s) of evaluation of this end point

4 years

4 anni

E.5.2

Secondary end point(s)

RECIST response rate
Overall Survival
Progression Free Survival
Clinical Benefit
Post-treatment Axitinib target status assessment

Risposta tumorale secondi i criteri RECIST
Tasso di sopravvivenza globale
Progressione libera da malattia (PFS)
Beneficio clinico
Status target di Axitinib (VEGFR e PDGFR) dopo trattamento

E.5.2.1

Timepoint(s) of evaluation of this end point

4 years

4 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

E.6.4

Safety

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

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)

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.8.5

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

The end of the trial is when all patients enrolled in the study completed the study treatment.

La fine delle sperimentazione è definito come il momento in cui tutti i pazienti arruolati nello studio hanno completato il trattamento di studio.

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.1.1.1

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)

Not applicable

Non applicabile

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

2014-03-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-01-28

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

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