Clinical Trials Register

Summary
EudraCT Number:	2016-003535-38
Sponsor's Protocol Code Number:	1447-STBSG
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-04-25
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2016-003535-38

A.3

Full title of the trial

Maintenance therapy with trabectedin versus observation after first line treatment with doxorubicin of patients with advanced or metastatic soft tissue sarcoma

A.3.1

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

Trabectedin maintenance post 1st-line in STS

A.4.1

Sponsor's protocol code number

1447-STBSG

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02929394

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	European Organisation for Research and Treatment of Cancer
B.1.3.4	Country	Belgium
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	Pharmamar
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	EORTC
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	European Organisation for the Research and treatment of Cancer
B.5.2	Functional name of contact point	Clinical Operations Department
B.5.3	Address:
B.5.3.1	Street Address	83/11 Avenue E. Mounier
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	1200
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003227741013
B.5.5	Fax number	003227741030
B.5.6	E-mail	regulatory@eortc.be

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.3.4	Pharmaceutical form	Powder for 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.3.8 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

Metastatic soft tissue sarcoma

E.1.1.1

Medical condition in easily understood language

Metastatic soft tissue sarcoma

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	19.1
E.1.2	Level	PT
E.1.2	Classification code	10075333
E.1.2	Term	Soft tissue sarcoma
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

The main objective of the trial is to evaluate whether maintenance trabectedin given after 6 cycles of doxorubicin first-line therapy for advanced or metastatic STS prolongs progression-free survival (PFS) as compared to an observational approach.

E.2.2

Secondary objectives of the trial

Secondary objectives are:
• To assess the treatment safety and tolerability
• To assess the efficacy of the treatment in terms of overall survival
(determined from randomization)
• To assess the time to second progression
• To compare the quality of life in patients randomized to the two study arms

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histologically proven locally advanced or metastatic high grade STS (excluding histologies insensitive to chemotherapy such as ASPS and PECOMA subtypes).
• Non-progressive disease (CR, PR or SD according to RECIST 1.1) after 6 cycles of first-line chemotherapy with doxorubicin for advanced and/or metastatic malignant STS.
• Interval from last dose of doxorubicin to randomization is maximum 6 weeks.
• Prior neoadjuvant or adjuvant non-anthracycline-chemotherapy is allowed, provided that the disease did not progress during neoadjuvant and/or adjuvant therapy or within 12 weeks after completion of the perioperative treatment.
• Representative formalin fixed, paraffin embedded tumor blocks or 10 unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. Histological central review is not required before treatment start but it is mandatory to send unstained tumor slides (blocks optional) at time of study entry. Local histopathological diagnosis will be accepted for entry into this trial.
• Age 18 years or older
• WHO performance status (PS) ≤ 1
• Adequate bone marrow, liver and renal function and coagulation parameters
• Normal cardiac function (LVEF assessed by MUGA or ECHO within normal range of the institution), normal 12 lead ECG (without clinically significant abnormalities).
• Recovery from toxicity (no more than Grade 1, except for alopecia)
• Evidence of post-menopausal status or for female pre-menopausal patients negative urinary or serum pregnancy test within 72 hours prior to first dose of study treatment. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• Women of childbearing potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months after the last study treatment. Men in fertile age must use effective contraception during treatment and 5 months after treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
Such methods include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
• Vasectomised partner
• Sexual abstinence
• Note: Trabectedin can have genotoxic effects. Advice on the possibility of ovules or sperm conservation should be given to the patient prior to start of treatment because of the possibility of irreversible infertility.
• Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 3 months after the last study treatment.
• Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

E.4

Principal exclusion criteria

• prior exposure to trabectedin
• active or uncontrolled infections or serious illnesses or medical conditions, including a • history of chronic alcohol abuse, hepatitis, HIV and/or cirrhosis.
• active brain metastases
• history, within the past five years, of malignancies other than soft tissue sarcoma (except: basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, resected incidental prostate cancer staged pT2 with Gleason Score ≤ 6 and postoperative PSA < 0.5 ng/ml). Patients with any history of malignancies who are disease-free for more than 5 years are eligible.
• any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial.

E.5 End points

E.5.1

Primary end point(s)

The primary end-point is progression-free survival defined from randomization until progression according to RECIST 1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

Tumor evaluations for the assessment of PFS will be done every 6 weeks during the first 6 months and every 12 weeks thereafter until PD or start of new treatment

E.5.2

Secondary end point(s)

Secondary end-points include:
• Safety and tolerability (Common Terminology Criteria for Adverse Events CTCAE 4.0)
• Overall survival
• Time to second progression (PFS2)
• Health related quality of life (QLQ-C30)

E.5.2.1

Timepoint(s) of evaluation of this end point

• Safety and tolerability
• Overall survival: every 6 weeks during the first 6 months; every 12 weeks thereafter until PD on first and on second line treatment; every 6 months thereafter until death.
• Time to second progression (PFS2): every 6 weeks during the first 6 months; every 12 weeks thereafter until PD on first and on second line treatment;
• Health related quality of life (QLQ-C30): within 7 days before randomization, every 6 weeks during the first 6 months and every 12 weeks thereafter until PD or start of new treatment

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

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

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

Observation

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

End of study occurs when all of the following criteria have been satisfied:
1. Thirty days after all patients have stopped protocol treatment
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis

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

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

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)

Patients in arm A (trabectedin maintenance) with documented PD will be taken off protocol therapy and may be treated with subsequent anticancer therapies or supportive care in accordance with each Institution standards.
Patients in arm B (observation) with documented PD are allowed to be treated with commercial trabectedin as per investigator's decision

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

2017-05-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-07-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-05-08

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