Clinical Trials Register

Summary
EudraCT Number:	2016-002186-56
Sponsor's Protocol Code Number:	2016/2410
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:	2016-10-20
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

2016-002186-56

A.3

Full title of the trial

Randomised phase III multicentric study comparing efficacy of doxorubicin with trabectedin followed by trabectedin in non-progressive patients versus doxorubicine alone as first-line therapy in patients with metastatic or unresectable leiomyosarcoma (uterine or soft tissue)

Étude de phase III multicentrique randomisée comparant l’efficacité de l’association doxorubicine et trabectédine, suivie de trabectédine seule en l’absence de progression, à celle de la doxorubicine seule, en traitement de première ligne des patients qui présentent un léiomyosarcome (utérin et des tissus mous) métastatique et/ou localement avancé

A.3.1

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

Study comparing efficacy of doxorubicin with trabectedin followed by trabectedin in non-progressive patients versus doxorubicine alone as first-line therapy in patients with metastatic or unresectable leiomyosarcoma (uterine or soft tissue)

Étude comparant l’efficacité de l’association doxorubicine et trabectédine, suivie de trabectédine seule en l’absence de progression, à celle de la doxorubicine seule, en traitement de première ligne des patients qui présentent un léiomyosarcome (utérin et des tissus mous) métastatique et/ou localement avancé

A.3.2

Name or abbreviated title of the trial where available

LMS04

A.4.1

Sponsor's protocol code number

2016/2410

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	GUSTAVE ROUSSY
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	PHARMA MAR
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GUSTAVE ROUSSY
B.5.2	Functional name of contact point	Service Promotion Etudes Cliniques
B.5.3	Address:
B.5.3.1	Street Address	114 rue Edouard Vaillant
B.5.3.2	Town/ city	Villejuif
B.5.3.3	Post code	94805
B.5.3.4	Country	France
B.5.4	Telephone number	FR +33142116198
B.5.5	Fax number	FR +33 142116290
B.5.6	E-mail	SPEC.Affaires.reglementaires@gustaveroussy.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	YONDELIS
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharma Mar S.A.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	trabectedin
D.3.4	Pharmaceutical form	Powder for solution for injection
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	TRABECTEDIN
D.3.9.1	CAS number	114899-77-3
D.3.9.4	EV Substance Code	SUB20756
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	1
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

Patients With Metastatic or Relapsed Unresectable Uterine or Soft Tissue Leiomyosarcoma

E.1.1.1

Medical condition in easily understood language

Patients With Metastatic or Relapsed Unresectable Uterine or Soft Tissue Leiomyosarcoma

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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10024191
E.1.2	Term	Leiomyosarcoma metastatic
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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10046799
E.1.2	Term	Uterine leiomyosarcoma
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

Determine and compare the progression-free survival (PFS) of patients treated in first line with doxorubicin alone or with the association of doxorubicin and trabectedin followed by trabectedin for non-progressive patients

E.2.2

Secondary objectives of the trial

Determine and compare for each arm :
1. Clinical benefice rate
2. Response rate
3. Duration of response
4. Toxicities.
5. Overall survival of patients
6. Progression-free survival in second line therapy (PFS2) after progression

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must have histologically confirmed diagnosis of metastatic or or relapsed, unresectable uterine or soft tissue leiomyosarcoma, reviewed in a reference center (among RREPS network), previously untreated with chemotherapy , and with available Formalin Fixed Paraffin Embedded (FFPE) blocks
2. At least one measurable lesion according to RECIST V 1.1 criteria. Target could be in a previously irradiated field but has to be progressive or a biopsy had to be positive before inclusion.
3. Age ≥ 18 years old
4. ECOG performance status < 2
5. Adequate haematological, liver and cardiac functions as defined in the protocol
6. Creatinin phosphokinase (CPK) ≤ 2.5 x ULN
7. Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days prior to inclusion. Both males and WOCBP who are sexually active should be using an effective birth control method from inclusion (for WOCBP) or treatment initiation (for male) and up to 6 months following the last dose of study drug.

E.4

Principal exclusion criteria

1. All other histological types of uterine sarcomas or soft tissue sarcomas
2. Any contraindication for the use of trabectedin and/or doxorubicin (cardiac, renal, hepatic, known hypersensitivity…)
3. History of another type of cancer not in complete remission for more than 3 years prior to study entry (except for cutaneous basal cell carcinoma or in situ cervical epithelioma), and/or having required any chemotherapy treatment at any time.
4. Known cerebral metastasis
5. History of allograft or autograft
6. Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection

E.5 End points

E.5.1

Primary end point(s)

RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

At baseline,
Every 6 weeks while on treatment period,
Every 9 weeks while on maintenance period or follow up period.

E.5.2

Secondary end point(s)

RECIST 1.1
NCI CTCAE Version 4

E.5.2.1

Timepoint(s) of evaluation of this end point

1. 2. 3. At baseline and then every 6 weeks up to 6 cycles of treatment.
4. All along the study
5. All along the study until patient death (including long term follow-up)
6. All along the study until progression under second line therapy

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

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)

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

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

Yes

E.8.2.3.1

Comparator description

background therapy

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

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 study is defined as being the last visit of the last patient at the end of the follow-up period or at the time 136 events will have been accumulated for analysis of the primary objective of the study, whichever is later (i.e around 2 years after the last patient inclusion).

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

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:

110

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

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

150

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

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

2016-08-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-19

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

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