Clinical Trials Register

Summary
EudraCT Number:	2014-004655-31
Sponsor's Protocol Code Number:	1143-SCCHN-202
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-04-09
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

France - ANSM

A.2

EudraCT number

2014-004655-31

A.3

Full title of the trial

Preoperative window-of-opportunity (WoO) study of Debio 1143 with or without cisplatin (CDDP) in patients with resectable squamous cell carcinoma of the head and neck.

Etude pré-opératoire exploratoire du Debio 1143 avec ou sans cisplatine chez des patients atteints d’un carcinome épidermoïde opérable de la tête et du cou

A.3.1

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

Study of Debio 1143 given with or without chemotherapy prior to head and neck cancer operation.

Etude du Debio-1143 avec ou sans cisplatine chez des patients atteints d’un carcinome de la tête et du cou avant leur opération.

A.3.2

Name or abbreviated title of the trial where available

Debio 1143-SCCHN-202

A.4.1

Sponsor's protocol code number

1143-SCCHN-202

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	Debiopharm International S.A.
B.1.3.4	Country	Switzerland
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	Debiopharm International S.A.
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Debiopharm International S.A.
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Chemin Messidor 5-7
B.5.3.2	Town/ city	Lausanne
B.5.3.3	Post code	1002
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	41213210111
B.5.5	Fax number	41213210169
B.5.6	E-mail	info-international@debiopharm.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	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	Debio 1143
D.3.2	Product code	1143
D.3.4	Pharmaceutical form	Capsule
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	{(5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide}
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	1143
D.3.9.3	Other descriptive name	Debio 1143
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	200
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.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	Yes
D.2.1.1.1	Trade name	Cisplatine Accord 1mg/ml, solution à diluer pour perfusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare France SAS
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Cisplatine Accord
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.3.11 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

Squamous cell carcinoma of the head and neck

E.1.1.1

Medical condition in easily understood language

Cancer of the head and neck

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	17.1
E.1.2	Level	PT
E.1.2	Classification code	10060121
E.1.2	Term	Squamous cell carcinoma of head and neck
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 investigate the pharmacodynamic activity of Debio 1143, alone or in combination with cisplatin, in patients with squamous cell carcinoma of the head and neck

E.2.2

Secondary objectives of the trial

To assess the safety profile of Debio 1143 alone and combined with cisplatin (CDDP).
To determine the safety on patient post operative bleeding and wound healing.
To assess the ability of to induce cellular apoptosis, and/or tumour necrosis and/or reduce tumour proliferation.
To assess any early evidence of biological response as evaluated by 18F-FDG PET;
To assess potential effect on immune signalling.
To explore plasma PK and tissue levels of Debio 1143 and its metabolite D-1143-MET1.
To explore potential PBs ( may include but not limited to DNA alterations, mRNA, and protein levels) that may be predictive of differences in response.
To explore genes that may be involved in DMET activity of Debio 1143 to identify potential genetic variations that may be predictive of differences in the PK .
To correlate 18F-FDG PET results with PK and PDy if deemed appropriate.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age 18 years and over.
2. Newly diagnosed histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx.
3. Patient selected for primary surgical treatment.
4. ECOG PS 0-1.
5. Neutrophil count > 1'500/mm3; platelet count > 75'000/mm3; WBC ≥ 3.0/10-9L; bilirubin or creatinine < 2 times ULN, ALAT or ASAT < 5 times ULN.
6. Women of childbearing potential:
a. Negative serum pregnancy test at screening;
b. Agreement to use appropriate contraception methods from study entry to 6 months after the last treatment day. Agreement from male partner to use contraception methods.
7. Male patient agreement to use contraception methods from study entry to 6 months after the last treatment day.
8. Signed informed consent

E.4

Principal exclusion criteria

1. Nasopharynx cancer, nasal cavity, and paranasal sinuses carcinomas, recurrent SCCHN.
2. Weight loss of more than 10% in the previous month.
3. Tumour of less than 2 cm in its largest diameter.
4. Distant metastases.
5. Active second malignancy during the last 5 years except non-melanomatous skin cancer or carcinoma in situ of the cervix.
6. Prior treatment with IAP inhibitors and TNF inhibitors.
7. Use or requirement for use of aspirin or aspirin-containing products with > 160 mg of aspirin per day.
8. Active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation.
9. Non-compensated liver cirrhosis (Child-Pugh class C).
10. Concomitant treatment with a drug on the prohibited medication list in Section 7.8.2.
11. Patients with known history of uncontrolled or symptomatic angina, arrhythmias or congestive heart failure.
12. If female, pregnant or lactating.
13. Unable to swallow and retain oral medications.
14. Know contraindication to 18F-FDG PET.

E.5 End points

E.5.1

Primary end point(s)

To assess the effect of Debio 1143 and Debio 1143 combined with CDDP on cIAP-1 levels in patients with SCCHN.

E.5.1.1

Timepoint(s) of evaluation of this end point

At end of study

E.5.2

Secondary end point(s)

1.Change in vital signs and ECOG PS.
2.Incidence of SAEs.
3.Incidence and severity of AEs graded according to the NCI-CTCAE v4 criteria.
4.Incidence and severity of laboratory abnormalities graded according to the NCI-CTCAE v4 criteria.
5.Rate of severe post-operative bleeding defined as decrease of haemoglobin (Hb) > 2 g/dL and clinical evidence of blood loss (eg, melaena, haematuria or surgical wound bleeding). Each case of Hb decrease > 2 g/dL with iron blood deficiency will be discussed between the Investigator and the Study Medical Monitor to decide whether the observed AE is related or not to post-surgical signs of bleeding.
6. Rate of delayed wound healing defined as presence of surgical wound or surgical wound healing complications at 3-4 weeks from surgery as per the Surgeon's judgment.
7. Assessment of the effect of Debio 1143 alone or combined with CDDP on apoptosis, and/or necrosis and/or proliferation markers in tumours.
8. Measurement of any early biological response to Debio 1143 alone or combined with CDDP by 18F-FDG PET.
9. Assessment of the effect of Debio 1143 alone or combined with CDDP on immune signalling.
10. PK parameters (Cmax, Tmax, AUC, T1/2, Ctrough, Cav, ARCmax, ARAUC, LIAUC, CL/F [only Debio 1143, V/F [only Debio 1143) of Debio 1143 alone and its metabolite D-1143-MET1 in plasma.
11. Tumour concentration distribution of Debio 1143 based on MALDI-MS method.
12. PK parameters (Cmax, AUC, CL) of free and total CDDP in plasma.
13. Visual predictive check of relationships between selected PK parameters and PDy and PGx markers.
14. Association of predictive markers with a PDy activity of Debio 1143.
15. Genetic variations in DMET genes associated with differences in the PK disposition of Debio 1143.
16. Exploration of relationships between 18F-FDG PET imaging results and PK/PDy markers if deemed appropriate.

E.5.2.1

Timepoint(s) of evaluation of this end point

At 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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Yes

E.8.1.7.1

Other trial design description

window of opportunity study

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

LPLV

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

Information not present in EudraCT

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)

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

2015-03-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-07-18

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