Clinical Trials Register

Summary
EudraCT Number:	2014-000256-28
Sponsor's Protocol Code Number:	LAP117314
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:	2015-06-22
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

2014-000256-28

A.3

Full title of the trial

A Randomised, Multicentre, Open Label, Phase II study of Prophylactic Octreotide to Prevent or Reduce the Frequency and Severity of Diarrhoea in Subjects Receiving Lapatinib with Capecitabine for the Treatment of Metastatic Breast Cancer.

A.3.1

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

A study to assess the use of Octreotide in the prevention or reduction of diarrhoea associated with lapatinib and capecitabine treatment in patients with metastatic breast cancer.

A.4.1

Sponsor's protocol code number

LAP117314

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	GlaxoSmithKline research & Development
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	GlaxoSmithKline R&D
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	GlaxoSmithKline Research & Development Ltd
B.5.2	Functional name of contact point	Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge Road, Stockley Park West
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 - 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 0208 990 44 66
B.5.5	Fax number	+44 0208 990 12 34
B.5.6	E-mail	GSKClinicalSupportHD@gsk.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	Yes
D.2.1.1.1	Trade name	Sandostatin® LAR® (10 mg, 20 mg or 30 mg powder and solvent for suspension for injection)
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharmaceuticals UK Limited
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
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	79517-01-4
D.3.9.3	Other descriptive name	OCTREOTIDE ACETATE
D.3.9.4	EV Substance Code	SUB03490MIG
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	40
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	Sandostatin (0.05mg/ml, 0.1 mg/ml, 0.5 mg/ml Ampoules and Multidose Vial 1 mg/5 ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS PHARMACEUTICALS UK LIMITED
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	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.3.9.1	CAS number	79517-01-4
D.3.9.3	Other descriptive name	OCTREOTIDE ACETATE
D.3.9.4	EV Substance Code	SUB03490MIG
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	0.1
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

Diarrhoea associated with treatment with lapatinib and capecitabine for metastatic breast cancer

E.1.1.1

Medical condition in easily understood language

Diarrhoea associated with treatment with lapatinib and capecitabine for metastatic breast 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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10027475
E.1.2	Term	Metastatic breast cancer
E.1.2	System Organ Class	100000004864

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 determine the efficacy of prophylactic octreotide in reducing the proportion of subjects experiencing diarrhoea with a severity of NCI CTCAE Grade 2 and above.

E.2.2

Secondary objectives of the trial

Determine the efficacy of prophylactic octreotide (Oct.) in reducing the:
-proportion of subjects experiencing diarrhoea with a severity of NCI CTCAE Grade 3 and above
-proportion of subjects experiencing diarrhoea of any grade of severity
-duration of diarrhoea of any grade of severity
-proportion of subjects taking antidiarrhoeal medication
-proportion of subjects making unscheduled visits to healthcare professionals as a result of diarrhoea
-proportion of subjects requiring changes in cancer therapy as a result of diarrhoea
-proportion of subjects requiring treatment with intravenous fluids resulting from diarrhoea
To determine the efficacy of prophylactic Oct. in reducing the increasing the time to onset of the first episode of diarrhoea of any grade of severity
Determine the efficacy of prophylactic Oct.on:
-compliance with lapatinib and capecitabine treatment
-the efficacy of treatment with lapatinib and capecitabine
-the safety and tolerability of cancer treatment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Deviations from the inclusion criteria are not allowed because they can potentially
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.
Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Signed written informed consent.
2. Histologically or cytologically confirmed HER2-positive advanced or metastatic
breast cancer which has progressed following prior therapy, which must have
included anthracyclines and taxanes and therapy with trastuzumab in the
metastatic setting.
3. Females age >or=18 years old.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 4)
5. Life expectancy of at least 12 weeks.
6. Able to swallow and retain oral medications.
7. Incapable of becoming pregnant, or not pregnant and using an adequate form of
contraception, i.e. a female who is of:
a. non-childbearing potential (physiologically incapable of becoming pregnant), including any female who has had hysterectomy, bilateral
oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for at least 1 year);
b. childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment with octreotide if randomised to receive octreotide or the first dose of lapatinib with capecitabine if randomised to receive no
octreotide, preferably as close to the first dose as possible, and must agree to use adequate contraception (intrauterine device, birth control pills unless clinically contraindicated, or barrier device) during the study and continuing for at least 4 weeks after the final dose of treatment with lapatinib and capecitabine.
8. Subjects must complete all screening assessments as outlined in the protocol.
9. Subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of octreotide if randomised to receive octreotide. All subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of lapatinib with capecitabine.
10. Prior treatment with other chemotherapeutic agents or endocrine therapy is permitted. All prior treatment related toxicities, except diarrhoea and alopecia,
must be NCI CTCAE (version 4.03) ≤ Grade 1 at the time of randomization.
Subjects with diarrhoea with any grade of severity within 14 days prior to randomisation are excluded from LAP117314.
11. Prior treatment with radiation therapy is permitted provided that at least 2 weeks
have elapsed since the last fraction of radiation therapy prior to treatment with octreotide if randomised to receive octreotide or the first dose of lapatinib with capecitabine if randomised to receive no octreotide, and all radiation therapy related AEs are ≤ Grade 1 at the time of randomization.
French subjects: In France, a subject will be eligible for inclusion in this study only if
either affiliated to or a beneficiary of a social security category. Other country-specific
criteria are included in Appendix 5.

E.4

Principal exclusion criteria

Deviations from exclusion criteria are not allowed because they can potentially
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.
Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Concurrent treatment with an investigational agent or concurrent participation in another clinical study.
2. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to treatment with octreotide for subjects randomised to receive octreotide or the first dose of lapatinib and capecitabine for subjects randomised to receive no octreotide.
3. Treatment with octreotide within the 3 months prior to randomization.
4. Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy
(including an EGFR and/or HER2 inhibitor), or hormonal therapy for treatment of cancer.
5. Dementia, altered mental status, or any psychiatric condition that would prohibit
the understanding or rendering of informed consent, unless a legally acceptable
representative could provide informed consent (if in accordance with the policies of the local Ethics Committee).
6. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety or compliance with study procedures.
7. Diarrhoea with any grade of severity within 14 days prior to treatment with
octreotide for subjects randomised to receive octreotide or within 14 days prior to the first dose of lapatinib and capecitabine for subjects randomised to receive no octreotide.
8. Malabsorption syndrome, inflammatory bowel disease (ulcerative colitis,
Chrohn’s disease), irritable bowel syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
9. Pregnant or lactating subjects.
French subjects: the French subject has participated in any study using an
investigational drug during the previous 30 days or 5 half-lives, whichever is longer,
preceding the first dose of protocol treatment.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects experiencing diarrhoea with a severity of Grade 2 and above, as defined by the NCI CTCAE, version 4.03.

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluated following 24 weeks of treatment with lapatinib and capecitabine

E.5.2

Secondary end point(s)

Investigator Reported
•Proportion of subjects experiencing diarrhoea with a severity of Grade 3 and above, as defined by the NCI CTCAE, version 4.03, recorded as AEs in the eCRF.
•Proportion of subjects experiencing diarrhoea of any grade of severity as defined by the NCI CTCAE, version 4.03, recorded as AEs in the eCRF.
•Duration of diarrhoea of any grade of severity, recorded as AEs in the eCRF.
•Time to onset of the first episode of diarrhoea of any grade of severity, recorded as an AE in the eCRF.
•Proportion of subjects taking anti-diarrhoeal medication, recorded in the eCRF.
•Proportion of subjects making diarrhoea-related unscheduled visits to healthcare professionals, recorded in the eCRF.
•Proportion of subjects requiring diarrhoea-related lapatinib and capecitabine dose reduction, dose delay and treatment withdrawal, recorded in the eCRF.
•Proportion of subjects requiring use of diarrhoea-related intravenous fluids for rehydration, recorded in the eCRF.
•Number of lapatinib and capecitabine tablets dispensed and returned, recorded in the eCRF.
•Overall response rate and clinical benefit response measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.
•Proportion of subjects with AEs and SAEs, recorded in the eCRF.

Subject Reported
•Proportion of subjects experiencing diarrhoea of any grade of severity, recorded in the diarrhoea diary.
•Time to onset of the first episode of diarrhoea of any grade of severity, recorded in the diarrhoea diary.
•Proportion of subjects taking anti-diarrhoeal medication, recorded in the diarrhoea diary.
•Proportion of subjects making dietary changes due to diarrhoea, recorded in the diarrhoea diary.
•Proportion of subjects making unscheduled visits to healthcare professionals due to diarrhoea, recorded in the diarrhoea diary.
•Proportion of subjects missing doses of lapatinib and capecitabine due to diarrhoea, recorded in the diarrhoea diary.

Quality of Life
•Proportion of subjects with improvement in quality of life, recorded by FACIT-D.

E.5.2.1

Timepoint(s) of evaluation of this end point

Evaluated following 24 weeks of treatment with lapatinib and capecitabine

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

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

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

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

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

Hong Kong

Israel

Russian Federation

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

A subject will be considered to have completed the study if the subject completes 24 weeks of treatment with lapatinib and capecitabine, or if cancer progresses or the subject dies during treatment, whichever is sooner.

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

140

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)

The investigator is responsible for ensuring that consideration has been given for the post-study care of the subject’s medical condition whether or not GSK is providing specific post-study treatment.
Refer to section 6.3 of Protocol 00 (page 61) for further details on the provision on Lapatanib and Capecitabine.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	CHILTERN
G.4.3.4	Network Country	France
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	ICTA

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-07-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-10-19

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