Clinical Trials Register

Summary
EudraCT Number:	2017-002561-21
Sponsor's Protocol Code Number:	IFCT-1604
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-02-02
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

France - ANSM

A.2

EudraCT number

2017-002561-21

A.3

Full title of the trial

Randomised Open Label Adaptive Phase III trial of addition of Belinostat to chemotherapy in patients with locally advanced potentially resectable Thymic Epithelial Tumors (TET)

A.3.1

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

Study of addition of belinostat to chemotherapy before surgery in patients with Thymic Epithelial Tumors (TET)

A.3.2

Name or abbreviated title of the trial where available

BELCAP

A.4.1

Sponsor's protocol code number

IFCT-1604

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	IFCT
B.1.3.4	Country	France
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	Onxeo
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IFCT
B.5.2	Functional name of contact point	Contact
B.5.3	Address:
B.5.3.1	Street Address	10 rue de la Grange-Batelière
B.5.3.2	Town/ city	PARIS
B.5.3.3	Post code	75009
B.5.3.4	Country	France
B.5.6	E-mail	contact@ifct.fr

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	Beleodaq (in the USA)
D.2.1.1.2	Name of the Marketing Authorisation holder	Spectrum Pharmaceuticals Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/13/1151
D.3 Description of the IMP
D.3.1	Product name	Belinostat
D.3.4	Pharmaceutical form	Powder 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	belinostat
D.3.9.1	CAS number	414864-00-9
D.3.9.3	Other descriptive name	PXD101
D.3.9.4	EV Substance Code	SUB121262
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	500
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

Locally advanced potentially resectable Thymic Epithelial Tumors

E.1.1.1

Medical condition in easily understood language

Locally advanced Thymus Tumors

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	10061031
E.1.2	Term	Thymoma malignant
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10026533
E.1.2	Term	Malignant neoplasm of thymus
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

To evaluate the efficacy of the induction treatment (after surgery and before any radiotherapy treatment) of adding belinostat to standard chemotherapy

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of the induction treatment (after surgery and before any radiotherapy treatment)
To evaluate the risk of relapse (local and/or regional relapse and/or distant metastasis) during the follow up period
To evaluate the long term overall survival
To evaluate overall tolerance
To evaluate quality of life

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacokinetic study : following pharmacokinetic parameters will be recorded both for belinostat and belinostat glucuronide: Cmax, Tmax, AUC (last, and inf), Half-life, Clearance (only for belinostat).
ECG and QT/QTc analysis : A 12 lead ECG will be done for central review in the patients participating in the PK study in the BEL CAP arm (15 patients planned) and, as possible, in 15 patients in the control CAP arm to assess cardiac tolerance.

E.3

Principal inclusion criteria

1. Histologically confirmed Thymoma (WHO classification A, AB, B1, B2, B3 ) or Thymic carcinoma.
The diagnosis of TET will be confirmed by a central expert tumour board based on the review of the tumor biopsy realized at site of the initial diagnosis; no new tumour biopsy is required for TET diagnosis.
2. Potentially resectable stage II-IVB (TNM IASLC-ITMIG 2014)
3. Age ≥ 18 years
4. WHO performance index of 0, 1
5. Adequate organ function
6. No previous treatment for TET
7. Signed informed consent form

E.4

Principal exclusion criteria

1. History of cancer except cancer dating from over three years ago and considered to be cured; appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma and stage I uterine cancer.
2. History of previous radiotherapy to the mediastinum
3. History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to any of the study drugs or their excipients
4. Decompensated Myasthenia Gravis
5. Significant cardiovascular disease of congestive heart failure Class III/IV to the NYHA Functional Classification, myocardial infarction within the past 6 months, unstable angina and unstable arrhythmia, left ventricular ejection fraction (LVEF) < 50% by either cardiac ultrasound or cardiac scintigraphy
6. Baseline prolongation of QT/QTc interval > 480ms for 7 or more days; long QT syndrome;
7. Concomitant use of strong UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) and concomitant medication that may cause Torsade de Pointes (refer to appendix I for list of drugs with known risk);
8. Pregnant or breast-feeding women; Women of childbearing age and potential who are not willing to use effective contraception during the study treatment period and until 30 days after last dose of study drug. Male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study treatment period and until 30 days after last dose of study drug.

E.5 End points

E.5.1

Primary end point(s)

% R0 Complete Resection in the two arms (experimental and control arms). R0 Complete Resection is defined as a complete resection of the primary tumor with no microscopic residual tumor (margins considered as microscopically negative: ≥ 1 mm) and complete macroscopic resection of pleural implants in stage IVA disease, assessed by a blinded pathologic central review.

E.5.1.1

Timepoint(s) of evaluation of this end point

After surgery (6 weeks after the last treatment)

E.5.2

Secondary end point(s)

% R0 Complete Resection assessed by the investigator’s site, with R0 defined as for the primary endpoint
% surgical resection of primary tumor defined as % of patients arriving to surgical resection after induction treatment
Pathological complete response (pCR) defined as % of patients with no microscopic residual tumor in the pathologic evaluation of the surgical specimen
Complete surgical resection by operative technique and boarding approach defined as % of R0 achieved by boarding approach (sternotomy-mediastinotomy-thoracothomy-videothoracoscopy-clamshell)
Objective Response Rate (ORR) defined as % of patients achieving a Response (complete response + partial response) after induction treatment according to RECIST 1.1 assessed by a Chest-CT Scan
DFS (Disease-Free Survival) defined as the time from the date of randomisation to the date of documented relapse or death of any cause. DFS will be estimated using the Kaplan-Meier method and plotted as curves by treatment group.
% Relapse defined as % of any relapse (local-regional-distant).
Pattern of relapse defined as % of relapse by anatomic sites and % of local versus regional versus distant relapse.
Post-operative morbidity and mortality defined as morbidity and mortality rate.
Other cancers defined as cancers other than TET.
To assess the impact of treatment toxicity until surgery by using QLQ-C30 LC13 and EQ-5D questionnaires.
To assess long term quality of life by using QLQ-C30 LC13 and EQ-5D questionnaires during the follow-up period

E.5.2.1

Timepoint(s) of evaluation of this end point

After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
After surgery (6 weeks after the last treatment)
4 weeks after the last treatment and before surgery
3 years, 5 years and 10 year
3 years, 5 years and 10 year
3 years, 5 years and 10 year
3 months
3 months
Until the end of the 10-year follow-up period
14 days before inclusion, before each cycle of treatment (week 1, week 4 and week 7), and at end of treatment visit (week 121) and post-surgery visit (6 weeks after surgery +/- 1 week 24).

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Adaptative

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

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

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

100

F.4.2.2

In the whole clinical trial

100

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)

None

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

2018-02-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-11

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

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