Clinical Trials Register

Summary
EudraCT Number:	2013-002564-69
Sponsor's Protocol Code Number:	410/56
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-01-28
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

Germany - PEI

A.2

EudraCT number

2013-002564-69

A.3

Full title of the trial

Double-blind, placebo-controlled multicenter phase II trial to evaluate the efficacy and safety of romiplostim for the treatment of chemotherapy-induced thrombocytopenia in subjects with relapsed ovarian cancer (2nd or further line)

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

T-RACE II

A.4.1

Sponsor's protocol code number

410/56

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	GMIHO Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
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	GMIHO Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Amgen
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	Charité Campus Virchow-Klinikum Universitätsmedizin Berlin
B.5.2	Functional name of contact point	Studiensekretariat
B.5.3	Address:
B.5.3.1	Street Address	Augustenburger Platz 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13353
B.5.3.4	Country	Germany
B.5.4	Telephone number	004930450564417

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	Nplate®
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Romiplostim
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ROMIPLOSTIM
D.3.9.1	CAS number	267639-76-9
D.3.9.3	Other descriptive name	ROMIPLOSTIM
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	625
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with relapsed ovarian cancer (2nd and 3rd line) treated with
chemotherapy according to AGO guidelines who develop
thrombocytopenia grade 3 and/or grade 4.

E.1.1.1

Medical condition in easily understood language

Severe reduction of platelets during chemotherapy in patients with
relapsed ovarian cancer

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	10066697
E.1.2	Term	Ovarian cancer recurrent
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 primary objective of the study is to evaluate the efficacy of secondary chemotherapy-induced thrombocytopenia prophylaxis with romiplostim in ovarian cancer subjects receiving myelosuppressive chemotherapy, with respect to platelet suppression during the first romiplostim/placebo cycle.

E.2.2

Secondary objectives of the trial

• To evaluate the safety of secondary chemotherapy induced thrombocytopenia prophylaxis with romiplostim in ovarian cancer subjects receiving myelosuppressive chemotherapy.
• To show advantageous results in the verum group with respect to other parameters related to platelets and supportive requirements.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Women ≥ 18 years of age
•Before any study-specific procedure, the appropriate written informed consent must be obtained, according to ICH-GCP, and national/local regulation
•ANC ≥ 1,000/μl, Hgb ≥ 9.5 g/dl, and platelet count ≥ 100 x 109/l on day 1 of the first on study cycle of the chemotherapy treatment (on-study cycle) (Thrombocytopenia have to be defined during a “qualifying cycle”; qualifying cycle could be the 1st or the 2nd cycle of the palliative chemotherapy; thrombocytopenia as evidenced by a platelet count < 50 x 109/l during the qualifying cycle of chemotherapy OR platelet count < 100 x 109/l on the
planned starting day of the next cycle of chemotherapy (or 1-3 days before),
requiring dose delay for platelet recovery.)
•Subjects with histologically confirmed advanced or metastatic ovarian cancer who are receiving 2nd or 3rd line chemotherapy consisting of one of the following regimens according to established dosing standards:
1. Topotecan, d 1-5, q3w
2. Gemcitabine, d1+8, q3w
3. Carboplatin / paclitaxel, d1, q3w
4. Carboplatin d1 / gemcitabine, d1+d8, q3w
5. Carboplatin /pegylated liposomal doxorubicin, d1, q4w
6. Carboplatin d1 / gemcitabine, d1+d8, Avastin d1, q3w
7. Topotecan d1-5 + avastin, q3w
8. Carboplatin + paclitaxel + avastin, q3w
•Thrombocytopenia as evidenced by a platelet count < 50 x 109/l during the qualifying cycle of chemotherapy OR platelet count < 100 x 109/l on the planned starting day of the next cycle of chemotherapy (or 1-3 days before), requiring dose delay for platelet recovery;
qualifying cycle could be the 1st or the 2nd cycle of chemotherapy
•Life expectancy ≥ 12 weeks at the time of screening
•Ability to receive the same dose and schedule of chemotherapy during the first on study treatment cycle as was given in the qualifying cycle(s). (In case of grade 4 thrombocytopenia: a dose reduction to ≥75% of the previous dose schedule is allowed.)

E.4

Principal exclusion criteria

•Previous treatment with PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), romiplostim, eltrombopag, or another thrombopoietic protein
•Past or current history of malignancies that affect the overall prognosis (Please note: patients with past or current malignancies not affecting the overall progonosis are allowed for enrolment)
•Subjects, who have had a larger surgery within the last 2 weeks before entering this study
•Subjects with an active infection; sepsis, disseminated intravascular coagulation, or any other condition (i.e. myelodysplastic syndrome {MDS}, immune thrombocytopenic purpura {ITP}, thrombotic thrombocytopenic purpura {TTP}, hemolytic uremic syndrome {HUS})
that may have exacerbated thrombocytopenia
•History of unstable angina, CHF {NYHA >class II}, uncontrolled hypertension {diastolic >100mm HG}, uncontrolled cardiac arrhythmia, or recent (within 1 year of screening) myocardial infarction (MI)
•History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 1 year of screening
•History of pulmonary embolism or other venous thrombosis within 1 year of screening (except for catheter-related clots)
•Receipt of any experimental therapy within the last 4 weeks prior to screening; subject is currently enrolled in, or has completed within the last 30 days, another investigational device or drug study (exception: PROVE study)
•Receipt of a bone marrow or peripheral blood stem cell infusion (within 1 year of screening)
•Positive pregnancy test
•Breast feeding period
•Reproductive potential and not using adequate highly effective methods of contraceptive precautions in the judgment of the investigator during treatment and for 6 month (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidial jelly)
•Known hypersensitivity to any recombinant E. Coli-derived product or any additives
•Inability to comply with the protocol or missing written informed consent
•Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and followup schedule; those conditions should be discussed with the subject before registration in the trial.
•Accommodation in an institution due to official or legal orders (§40 p. 1 No. 4 AMG)

E.5 End points

E.5.1

Primary end point(s)

To compare the rate of grade 3 to 4 thrombocytopenia in the first
treatment cycle (after the qualifying one) by treatment group (nadir value
of the platelet counts measured on days 8, 11 or 12, 15 and 18 or 19
[days 18 or 19 are obligatory in cycle 1 only]) as the major efficacy
endpoint (with the sample size calculation to be based upon).

E.5.1.1

Timepoint(s) of evaluation of this end point

After study medication application

E.5.2

Secondary end point(s)

The rate of adverse events of grade 3/4 in the first four on-study
cycles between the experimental arm and the placebo arm
On-study cycle is defined as every therapy cycle after initiation of
investigational product.
· The rate of grade 3/4 thrombocytopenia in each treatment cycle by
treatment group (nadir value of the platelet counts measured on days
AG62 / V. 1.0 / 23.04.2013 - 4 -
Romiplostim in recurrent ovarian cancer
8, 11 or 12, 15 and 18 or 19 [days 18 or 19 are obligatory in cycle 1
only])
· The average platelet nadir per cycle for each subject in each
treatment group during the study (determination of platelet counts on
days 8, 11 or 12, 15 and 18 or 19 [days 18 or 19 are obligatory for
cycle 1 only])
· The proportion of patients suffering from grade 1, 2, 3, or 4 bleeding
events (maximum NCI CTC grade by patient) during on study
chemotherapy treatment cycles by treatment group
· The proportion of subjects in each treatment group who experience
grade 1, 2, 3, or 4 thrombocytopenia (maximum NCI CTC grade by
patient) during on study chemotherapy treatment cycles
· The duration of grade 3/4 thrombocytopenia experienced during on
study chemotherapy treatment cycles.
· The number of subjects in each treatment group who are
administered platelet transfusions and the rate of administered
platelet transfusions during study chemotherapy treatment cycles
· The platelet count on day 22 of the on study chemotherapy treatment
cycles by treatment group
· The proportion of subjects able to receive all CT cycles on time by
treatment group
· ADR and SADR of romiplostim

E.5.2.1

Timepoint(s) of evaluation of this end point

End of study for all patients

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

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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

30 days after last study drug application

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

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.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)

No study-specific follow-up treatment is defined. Patients will be
treated after end of study according to the national guidelines for
ovarain cancer patients.

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

2014-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-04-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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