Clinical Trials Register

Summary
EudraCT Number:	2009-016858-41
Sponsor's Protocol Code Number:	E7080-G000-204
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-03
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2009-016858-41

A.3

Full title of the trial

An Open-Label, Single-Arm, Multicenter Phase 2 Study of E7080 in Subjects with Advanced Endometrial Cancer and Disease Progression Following First-Line Chemotherapy

Az E7080 vizsgálati készítmény, nyílt, egykarú, többközpontú, Fázis II vizsgálata előrehaladott endometriumrákban szenvedő és az elsővonalbeli kemoterápiát követően progressziót mutató betegeknél

A.3.1

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

A clinical study of a new drug called E7080 for patients with cancer of the womb that has spread to other parts of the body after having one platinum based chemotherapy. The patients know they are receiving the drug. The study is being done in different countries and the safety and effectivenes of E7080 have already been studied in other cancer patients.

Egy E7080 nevű új készítmény klinikai vizsgálata olyan betegek kezelésére, akiknél a méhrák egy platina alapú kemoterápia után átterjedt a test más területeire. A betegek tudnak róla, hogy ezt a készítményt kapják. A vizsgálat a világ több különböző országában folyik, az E7080 biztonságosságát és hatékonyságát pedig vizsgálták már más rákos betegeknél.

A.3.2

Name or abbreviated title of the trial where available

HOPE

A.4.1

Sponsor's protocol code number

E7080-G000-204

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	Eisai Ltd.
B.1.3.4	Country	United Kingdom
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	Eisai Ltd.
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PSI-CRO Hungary Pharma Support Ltd.
B.5.2	Functional name of contact point	RA Budapest
B.5.3	Address:
B.5.3.1	Street Address	Szabadsag ter 7. 3 em.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	H-1054
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3615556755
B.5.5	Fax number	+3615556750
B.5.6	E-mail	rabudapest@psi-cro.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	Lenvatinib
D.3.2	Product code	E7080
D.3.4	Pharmaceutical form	Capsule, hard
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	Lenvatinib
D.3.9.2	Current sponsor code	E7080
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	4
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	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	Lenvatinib
D.3.2	Product code	E7080
D.3.4	Pharmaceutical form	Capsule, hard
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	Lenvatinib
D.3.9.2	Current sponsor code	E7080
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	10
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

Unresectable endometrial cancer and disease progression following platinum-based, first-line chemotherapy

Nem operabilis, előrehaladott endometriumrák az elsővonalbeli kemoterápiát követően progressziót mutató betegségben.

E.1.1.1

Medical condition in easily understood language

Advanced endometrial cancer that has been treated previously, but has not responded, or has got worse despite treatment.

Előrehaladott endometriumrák, amit korábban már kezeltek, de a betegség vagy nem változott, vagy a kezelés ellenére rosszabbodott.

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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10014740
E.1.2	Term	Endometrial cancer stage III
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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10014736
E.1.2	Term	Endometrial cancer recurrent
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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10014734
E.1.2	Term	Endometrial cancer 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	14.0
E.1.2	Level	PT
E.1.2	Classification code	10014741
E.1.2	Term	Endometrial cancer stage IV
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 assess the objective response rate (ORR: complete response + partial response [CR+ PR]) of E7080 in subjects with unresectable endometrial cancer and disease progression following platinum-based, first-line chemotherapy.

E.2.2

Secondary objectives of the trial

To assess progression-free survival (PFS) and overall survival (OS) of subjects in this study population when treated with E7080.To assess the disease control rate (DCR: CR + PR + stable disease [SD ≥7 weeks]);
clinical benefit rate (CBR: CR + PR + durable SD [SD ≥23 weeks]); and durable SD rate.To assess the safety and tolerability of E7080. To assess the pharmacokinetic (PK) profile and pharmacodynamics of E7080 in subjects with advanced endometrial cancer.

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

MRI assessment sub-study

E.3

Principal inclusion criteria

1) Histologically confirmed diagnosis of endometrial carcinoma.
2)Radiographic evidence of disease progression according to RECIST 1.1(Appendix 1) after 1 prior
systemic, platinum-based chemotherapy regimen for metastatic or primary unresectable endometrial carcinoma for which no surgical or radiotherapy treatment options exist. Patients with disease progression within 1 year following completion of platinum-based chemotherapy administered as either
adjuvant or neoadjuvant treatment will be eligible without the requirement for further systemic treatment. Patients who have received platinum-based adjuvant
or neoadjuvant treatment and have disease progression more than 1 year following treatment must receive 1 additional cytotoxic systemic treatment before being
eligible for enrollment in this study (revised per Amendment 02).
3) Measurable disease meeting the following criteria:
─ At least 1 lesion of ≥1.0 cm in the longest diameter for a non-lymph node or ≥1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). If there is only 1 target
lesion, and it is a non-lymph node, it should have a longest diameter of ≥1.5 cm (revised per Amendment 02).
─ Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of
progressive disease based on RECIST 1.1 to be deemed a target lesion.
4) Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Appendix 2).
5) Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit (revised per Amendment 01).
6) Adequate renal function defined as calculated creatinine clearance ≥30 mL/min per the Cockcroft and Gault formula (Appendix 3) (revised per Amendment 01).
7) Adequate bone marrow function:
─ Absolute neutrophil count (ANC) ≥1000/mm3 (≥1.0 x 103/μ/L);
─ Platelets ≥100,000/mm3 (≥100 x 109/L);)
─ Hemoglobin ≥9.0 g/dL
8) Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤1.5.
9) Adequate liver function:
─ Bilirubin ≤1.5 x the upper limit of normal (ULN) except for unconjugated hyperbilirubinaemia of Gilbert’s syndrome;
─ Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN (≤5 x ULN if subject has liver metastases).
10) Females age ≥18 years at the time of informed consent.
11) Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [ß-hCG] test with a
minimum sensitivity of 25 IU/L or equivalent units of ß-hCG). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug. (revised per Amendment 02)
12) All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing) (revised per Amendment 02).
13) Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a
contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after
study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during
the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation (Revised per Amendment 02).
14) Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

E.4

Principal exclusion criteria

1) Brain or leptomeningeal metastases, including stable metastases (added per Amendment 01).
2) More than 1 prior systemic chemotherapy regimen for metastatic or primary unresectable endometrial carcinoma or any treatment targeting vascular endothelial
growth factor (VEGF)-directed angiogenesis. There is no restriction regarding prior hormonal therapy (revised per Amendment 02).
3) Prior systemic anti-tumor therapy within 3 weeks.
4) Not fully recovered from prior radiotherapy based on investigator judgment(added per Amendment 01).
5) Subjects with >1+ proteinuria on urine dipstick will undergo 24-hour urine collection for quantitative assessment of proteinuria (revised per Amendments 01 and 02). Subjects with 24-hour urine protein ≥1 g will be ineligible.
6) Gastrointestinal malabsorption or any other condition that might affect the absorption of E7080.
7) Inability to take oral medication.
8) Major surgery within 3 weeks prior to the first dose of study drug.
9) Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II (Appendix 4); unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment.
10) Prolongation of QTc interval to >480 msec.
11) Bleeding disorder or thrombotic disorder requiring anticoagulant therapy, such as warfarin, or similar agents requiring therapeutic INR monitoring (treatment with low molecular weight heparin [LMWH] is allowed).
12) Active hemoptysis (bright red blood of at least ½ teaspoon) within 3 weeks prior to the first dose of study drug.
13) Known intolerance to the study drug (or any of the excipients).
14) Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
15) Any malignancy (except for endometrial cancer, basal or squamous cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix) in the past
2 years (revised per Amendments 01 and 02).
16) Previous treatment with an investigational drug within 30 days prior to the first dose of study drug.
17) Females who are pregnant or breastfeeding.

E.5 End points

E.5.1

Primary end point(s)

Objective tumour response rate (CR + PR) based on modified RECIST 1.1

E.5.1.1

Timepoint(s) of evaluation of this end point

Disease control rate (CR + PR + SD) based on RECIST 1.1 and minimum duration
of SD lasting ≥7 weeks.

E.5.2

Secondary end point(s)

Progression-free survival based on RECIST 1.1 and measured as the time from the
date of first treatment until the date of first documentation of disease progression or
date of death, if death occurs prior to disease progression.

E.5.2.1

Timepoint(s) of evaluation of this end point

Clinical benefit rate (CR + PR + durable SD) based on RECIST 1.1 and SD lasting
≥23 weeks.
Durable SD rate based on RECIST 1.1 and defined as SD lasting ≥23 weeks.

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

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

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Bulgaria

Hungary

Poland

Romania

Russian Federation

Ukraine

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

Last patient, last visit

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

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

130

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)

Subjects who are receiving study drug at the end of the Treatment Phase will continue to receive study drug during treatment cycles in the Extension Phase. Subjects will remain on treatment in consecutive 28-day (4-week) cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or discontinuation of E7080 development by the Sponsor. Off-treatment assessments will occur within 30 days following the final study treatment.

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

2010-10-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-07-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-10-10

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