Clinical Trials Register

Summary
EudraCT Number:	2015-002629-21
Sponsor's Protocol Code Number:	SOFT
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:	2021-01-26
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

2015-002629-21

A.3

Full title of the trial

Phase II study on Regorafenib in advanced Solitary Fibrous Tumor

Studio di fase 2 su Regorafenib nel tumore fibroso solitario avanzato

A.3.1

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

Phase II study on Regorafenib in advanced Solitary Fibrous Tumor

Studio di fase 2 su Regorafenib nel tumore fibroso solitario avanzato

A.3.2

Name or abbreviated title of the trial where available

SOFT

A.4.1

Sponsor's protocol code number

SOFT

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 DEI 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 dei Tumori
B.5.2	Functional name of contact point	clinical trial center
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	0039 02 2390 3287
B.5.5	Fax number	0039 02 2390 3353
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	STIVARGA - 40 MG - COMPRESSE RIVESTITE CON FILM - USO ORALE - FLACONE (HDPE) - 28 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BAYER PHARMA AG
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	stivarga
D.3.2	Product code	BAY 73-4506
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	regorafenib
D.3.9.1	CAS number	755037-03-7
D.3.9.2	Current sponsor code	BAY 73-4506
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
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

Solitary Fibrous Tumor

tumore fibroso solitario

E.1.1.1

Medical condition in easily understood language

Solitary Fibrous Tumor

tumore fibroso solitario

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10068771
E.1.2	Term	Soft tissue neoplasm
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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Overall tumor Response Rate, according to Choi criteria extended even to MRI

determinazione della proporzione di riposte definite in base a criteri Choi, estesi anche alla risonanza magnetica

E.2.2

Secondary objectives of the trial

RECIST response rate
Overall Survival
Progression Free Survival
Clinical Benefit Rate
Safety

- determinazione della proporzione di risposte -secondo i criteri RECIST
- sopravvivenza totale
- tempo libero da progressione di malattia
- beneficio clinico definito come la somma delle risposte complete, parziali e delle stabilizzazioni di malattia secondo RECIST dopo 6 mesi dall¿avvio del trattamento
- profilo di sicurezza del farmaco

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Histological centrally confirmed diagnosis of solitary fibrous tumor
- 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 with Choi criteria
- Evidence of progression by Choi during the 6 months before study entry
- 1st, 2nd or 3rd line
- Eastern Cooperative Oncology Group (ECOG) Performance Status = 2
- Adequate bone marrow function, defined as the following: WBC >3.0 x 109/L,
ANC >1.5 x 109/L, platelets >100 x 109/L, Hb >9 g/dL and blood transfusions to reach the baseline requested Hb level are not allowed
- Adequate organ function, defined as the following: total bilirubin <1.5 times the upper limit of normal (except in case of Gilbert’s syndrome), AST (SGOT) and ALT (SGPT) <2.5 x UNL, Lipase = 1.5 x the ULN, 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; alkaline phosphatase <2.5 x ULN (<5 x upper limit of normal for patients with liver involvement of their cancer and/or have bone metastases); PT-INR/PTT <1.5 x upper limit of normal (Patients who are being therapeutically anti-coagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists).
- Cardiac ejection fraction =50% as measured by echocardiogram
- 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 amenorrhoeic 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.

- diagnosi patologica di tumore fibroso solitario, confermata centralmente
- malattia localmente avanzata o metastatica
- malattia valutabile secondo i criteri Choi
- evidenza di progressione secondo Choi nei 6 mesi precedenti all’ingresso nello studio
- prima, seconda o terza linea di trattamento
- Eastern Cooperative Oncology Group (ECOG) Performance Status = 2
- Adeguata funzionalità midollare definite come: globuli bianchi >3.0 x 109/L, numero assoluto di neutrofili >1.5 x 109/L, piastrine >100 x 109/L, emoglobina >9 g/dL (non è ammesso eseguire trasfusioni per raggiungere i livelli richiesti di emoglobina)
- Adeguata funzionalità d’organo, definita come: bilirubina totale <1,5 volte il limite superiore della norma (UNL), AST (SGOT) e ALT (SGPT) <2,5 x UNL, lipasi = 1,5 x ULN, creatinina <1,5 x ULN. Creatinina clearance entro i limiti istituzionali normali o creatinina clearance ¿ ¿60 ml / min / 1,73 m2; fosfatasi alcalina <2,5 x ULN (<5 x UNL per i pazienti con coinvolgimento epatico e / o hanno metastasi ossee); PT-INR / PTT < 1.5 x UNL (sarà consentita la partecipazione ai pazienti in terapia con farmaci come Coumadin o eparina a condizione che non vi siano alterazioni dei valori della coagulazione
- Frazione di eiezione cardiaca =50%
- I pazienti di sesso femminile in età fertile devono avere un test di gravidanza negativo effettuato entro i 7 giorni dall’avvio della prima somministrazione del farmaco in studio. Le donne in post-menopausa devono avere una amenorrea da almeno 12 mesi. Pazienti di sesso maschile e di sesso femminile potenzialmente fertili devono accettare di utilizzare un metodo efficace di controllo delle nascite durante tutto la durata dello studio e per un massimo di 3 mesi dopo la sospensione del farmaco in studio.
- Storia clinica negativa per eventi tromboembolici occorsi negli ultimi di 12 mesi

E.4

Principal exclusion criteria

- Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing.
- Prior treatment with >3 lines of anticancer agents
- 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 radiation therapy within 14 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 4 weeks prior to study entry
- Pregnancy
- Brest feeding
- Inability to swallow oral tablets (crushing of study treatment tablets is not allowed)
- Evidence of congestive heart failure classified as New York Heart Association Class 2 or higher
- Evidence of unstable angina (angina symptoms at rest) or new-onset angina = 3 months prior to screening.
- Medical history of a myocardial infarction < 6 months prior to initiation of study treatment
- Arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
- Uncontrolled hypertension (systolic blood pressure [SBP] > 140 mmHg or diastolic blood pressure [DBP] > 90 mmHg) despite optimal medical management
- Medical history of arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment
- Ongoing infection with severity of Grade 2 or above (NCICTCAE v 4.0)
- Known history of human immunodeficiency virus infection
- Active or chronic hepatitis B or C requiring treatment with antiviral therapy
- History of organ allograft
- Evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity
- Medical history of hemorrhage or a bleeding event = Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment
- Presence of non-healing wound, ulcer, or bone fracture
- Renal failure requiring hemodialysis or peritoneal dialysis
- Dehydration = Grade 1 (NCI-CTCAE v 4.0)
- Interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained
- Persistent proteinuria > 3.5 g/24 hours measured by urine protein creatinine ratio from a random urine sample (= Grade 3, NCICTCAE v 4.0)
- Evidence of any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject’s participation in the study or evaluation of the study results
- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
- Presence of any malabsorption condition
- Previous radiotherapy to 25 % of the bone marrow
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Regorafenib
- Expected non-compliance to medical regimens

- Precedente trattamento con altri farmaci oncologici entro 14 giorni dal primo giorno di somministrazione del farmaco in studio
- Più di 3 linee di trattamento antitumorale precedente
- Diagnosi di altro tumore maligno primitivo entro i 5 anni precedenti, ad eccezione del basalioma della cute, del carcinoma in situ della cervice uterina, o altre neoplasie che comportano un basso rischio di recidiva
- Trattamento con radioterapia entro i 14 giorni che precedono il primo giorno di somministrazione del farmaco in studio
- Mancato recupero da eventi avversi causati da agenti somministrati più di 4 settimane prima dal primo giorno di somministrazione del farmaco
- Chirurgia maggiore nelle 4 settimane precedenti l'ingresso nello studio
- Gravidanza
- Allattamento
- Incapacità a deglutire le compresse per via orale (la frantumazione di compresse di regorafenib non è consentita)
- Prova di insufficienza cardiaca congestizia classificata come classe 2 o superiore secondo New York Heart Association
- Prove di angina instabile (sintomi di angina a riposo) o di nuova insorgenza di angina = 3 mesi prima dello screening.
- Anamnesi di un infarto del miocardio <6 mesi prima dell'inizio del trattamento in studio
- Aritmie che richiedono terapia anti-aritmica, con l'eccezione di betabloccanti o digossina
- Ipertensione non controllata (pressione sistolica [SBP]> 140 mmHg o pressione diastolica [DBP]> 90 mmHg), nonostante trattamento medico ottimale
- Anamnesi di eventi trombotici arteriosi o eventi embolici o eventi cerebrovascolari (inclusi attacchi ischemici transitori) o embolia polmonare, nei 6 mesi precedenti l'inizio del trattamento in studio
- Infezione in corso con grado 2 o superiore (NCICTCAE v 4.0)
- Storia nota di infezione da virus dell'immunodeficienza umana
- Epatite B o C attiva o cronica che richieda un trattamento con terapia antivirale
- Storia di trapianto d’organo
- Evidenza o storia di qualsiasi diatesi emorragica (compresa l'emofilia lieve), a prescindere dalla gravità
- Anamnesi di emorragia o episodio di sanguinamento = grado 3 (NCI-CTCAE v 4.0) entro 4 settimane dall'inizio del trattamento in studio
- Presenza ferite non guarite, ulcere o di fratture ossee
- Insufficienza renale che necessita di emodialisi o dialisi peritoneale
- Disidratazione = Grado 1 (NCI-CTCAE v 4.0)
- Presenza di malattia polmonare interstiziale sintomatica all’atto della firma del consenso informato
- Proteinuria persistente >3,5 g/ 24 ore, calcolata come rapporto creatinuria/proteinuria in un campione di urine estemporaneo (= grado 3, NCICTCAE v 4.0)
- Presenza di qualsiasi altra malattia grave o instabile, o condizione medica, psicologica o sociale, che potrebbe compromettere la sicurezza del soggetto e/o il suo/la sua conformità alle procedure dello studio, o che può interferire con la partecipazione del soggetto allo studio o con la valutazione dei risultati dello studio
- Ipersensibilità nota al farmaco dello studio, o alla classe farmaceutica a cui appartiene, o a eccipienti presenti nella formulazione del farmaco
- Presenza di qualsiasi condizione di malassorbimento
- Precedente radioterapia sul 25% del midollo osseo
- Storia di reazioni allergiche attribuite a composti chimici o a composizione biologica simile a regorafenib
- Mancata adesione al trattamento medico proposto

E.5 End points

E.5.1

Primary end point(s)

Overall tumor Response Rate, according to Choi criteria extended even to MRI

determinazione della proporzione di riposte definite in base a criteri Choi, estesi anche alla risonanza magnetica

E.5.1.1

Timepoint(s) of evaluation of this end point

3 years

3 anni

E.5.2

Secondary end point(s)

RECIST response rate; Overall Survival; progression free survivol; Clinical Benefit Rate; Safety

determinazione della proporzione di risposte -secondo i criteri RECIST; sopravvivenza totale; tempo libero da progressione di malattia; beneficio clinico definito come la somma delle risposte complete, parziali e delle stabilizzazioni di malattia secondo RECIST dopo 6 mesi dall¿avvio del trattamento; profilo di sicurezza del farmaco

E.5.2.1

Timepoint(s) of evaluation of this end point

3 years; 6 years; 6 years; 6 months; 6 years

3 anni; 6 anni; 6 anni; 6 mesi; 6 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

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.8.4.1

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

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

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

2015-07-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-23

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

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