Clinical Trials Register

Summary
EudraCT Number:	2018-003650-24
Sponsor's Protocol Code Number:	20328
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:	2020-10-07
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

2018-003650-24

A.3

Full title of the trial

A single arm, open-label, multicenter Phase 2 study of regorafenib in participants who have been treated in a previous Bayer-sponsored regorafenib study (monotherapy or combination treatment) that has reached the primary completion endpoint or the main data analysis, or has been stopped prematurely.

Studio a braccio singolo, in aperto, multicentrico, di fase 2 su regorafenib in partecipanti trattati in un precedente studio su regorafenib promosso da Bayer
(in monoterapia o in combinazione) che abbia raggiunto l’endpoint di completamento primario o l’analisi principale dei dati oppure sia stato interrotto anticipatamente

A.3.1

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

Regorafenib rollover study

Studio Regorafenib rollover

A.3.2

Name or abbreviated title of the trial where available

Regorafenib rollover study

A.4.1

Sponsor's protocol code number

20328

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	BAYER AG
B.1.3.4	Country	Germany
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	Bayer AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	Muellerstraße 178
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.6	E-mail	clinical-trials-contact@bayer.com

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 film-coated tablets
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer 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 40 mg film-coated tablets
D.3.2	Product code	[na]
D.3.4	Pharmaceutical form	Film-coated 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	Regorefenib
D.3.9.1	CAS number	755037-03-7
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	na
D.3.9.4	EV Substance Code	SUB73090
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.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	No
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	Regorafenib
D.3.2	Product code	[BAY 73-4506 TABL 20MG 122 COAT]
D.3.4	Pharmaceutical form	Film-coated 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	na
D.3.9.4	EV Substance Code	SUB73090
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	20
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

1. metastatic or unresectable renal cell cancer (RCC)
2. metastatic and/or unresectable gastrointestinal stromal tumors (GIST)
3. metastatic colorectal cancer (CRC)
4. hepatocellular carcinoma (HCC)

carcinoma tipo RCC
carcinoma tipo GIST
carcinoma tipo CRC
carcinoma tipo HCC

E.1.1.1

Medical condition in easily understood language

Patients with a solid tumor treated previously with regorafenib (monotherapy or combination treatment) are eligible.

Pazienti con tumori solidi precedentemente trattati con regorafenib (in monoterapia o trattamento combinato)

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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10038407
E.1.2	Term	Renal cell cancer
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

• The primary purpose of the program is to enable participants, currently receiving regorafenib in a Bayer sponsored clinical trial and assessed by the PI to be benefitting, to continue regorafenib treatment after their respective study has met its primary completion date, or main data analysis, or has been stopped prematurely.
• And the documentation of safety

La finalità principale del programma è consentire ai partecipanti attualmente trattati
con regorafenib nell’ambito di una sperimentazione clinica promossa da Bayer e per
i quali il medico sperimentatore (PI) ritenga benefico il trattamento con regorafenib,
di proseguire lo stesso, una volta che il relativo studio ha raggiunto l’endpoint di
completamento primario o l’analisi principale dei dati oppure è stato interrotto
anticipatamente.
¿ E la documentazione sul profilo di sicurezza

E.2.2

Secondary objectives of the trial

Documentation of tolerability

Documentazione sulla tollerabilità

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age
1. Participant must be age-eligible in the feeder study at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Participant is currently participating in any Bayer-sponsored regorafenib study and is receiving study treatment.
3. Participant is currently benefiting from treatment with regorafenib monotherapy and meets criteria to initiate a subsequent cycle of therapy, as determined by the guidelines of the feeder protocol.
4. Any ongoing adverse events that require temporary treatment interruption must be resolved to baseline grade or assessed as stable and not requiring further treatment interruption by the investigator.
Sex
5. Male or female
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. This applies for the time between signing of the informed consent form and 2 months after the last administration of the study intervention.
Male participants:
In addition to the above methods, male trial participants and male partners of female trial participants must also use condoms during sex as an extra measure of protection against pregnancy.
Female participants:
The investigator or a designated associate is requested to advise sexually active participants on how to achieve highly effective birth control using one or more of the following methods:
• Hormonal contraception associated with inhibition of ovulation containing both estrogen and progestogen (oral, intravaginal or transdermal)
• Hormonal contraception associated with inhibition of ovulation containing only progestogen (oral, injectable or implantable)
• Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomized partner (provided that partner is the sole sexual partner of the woman of childbearing potential who is the trial participant and that the vasectomized partner has received medical assessment of surgical success)

Women not considered to be of childbearing potential include those who biologically sterile, permanently sterilized (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy) or postmenopausal. Postmenopausal women are defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
Informed Consent
6. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

E.4

Principal exclusion criteria

Medical Conditions
1. Ineligibility, for medical reasons, to start the next cycle in the respective feeder study
2. Patients with a beta-hCG test consistent with pregnancy.
Prior/Concomitant Therapy
3. Participants are using one or more of the prohibited medications listed in the respective feeder study protocol. A comprehensive list can be found in Section 6.4.
Prior/Concurrent Clinical Study Experience
4. Participant has been previously permanently discontinued from regorafenib treatment.
Diagnostic assessments
Not Applicable for this study.
Other Exclusions
5. Participant is unable to comply with the requirements of the study.

E.5 End points

E.5.1

Primary end point(s)

• Frequency and severity of SAEs and protocol-specified AEs

E.5.1.1

Timepoint(s) of evaluation of this end point

All safety analysis will be done in a descriptive manner only at the end of study.

E.5.2

Secondary end point(s)

• Frequency of dose modifications.

E.5.2.1

Timepoint(s) of evaluation of this end point

Tolerability of the study drug will be evaluated by displaying the number of dose modifications in frequency tables at the end of study.

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

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)

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

Yes

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

China

France

Germany

Italy

Japan

United Kingdom

United States

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 study is defined as the date when the last participant has completed the study and the sponsor has decided to close enrollment.

LPLV/decisione dello Sponsor di concludere l'arruolamento

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

Yes

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)

A subject which has ended the participation in this trial will be treated according to local guidelines for the treatment of his disease.

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

2019-02-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-12

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

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IMP with orphan designation in the indication
Orphan Designation Number:
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