Study of Prophylactic Octreotide to Prevent or Reduce the... | NCT02294786

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Octreotide treatment	Experimental	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.	Drug: Lapatinib Drug: Capecitabine Drug: Octreotide
No Octreotide treatment	Experimental	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment	Drug: Lapatinib Drug: Capecitabine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Lapatinib	Drug	Lapatinib was supplied as 250mg tablets that are oval, biconvex, and orange film-coated with one side plain and the opposite side debossed, or as 250mg tablets that are oval, biconvex, and yellow film-coated with one side plain and the opposite side debossed. Each tablet contained 405mg of Lapatinib ditosylate monohydrate, equivalent to 250mg Lapatinib free base

Measure	Description	Time Frame
Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks)	Proportion of subjects experiencing at least one episode of diarrhoea with a severity of Grade 2 and above, as defined by the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 4.03, recorded as AEs in the Electronic case report form (eCRF)	Up to 24 weeks

Measure	Description	Time Frame
Proportion of Subjects Experiencing Diarrhoea of Grade 3 and Above (up to 24 Weeks)	Proportion of subjects experiencing diarrhoea with a severity of Grade 3 and above, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF	Up to 24 weeks
Proportion of Subjects Experiencing Diarrhoea of Any Grade of Severity (up to 24 Weeks)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed written informed consent
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
Females age >=18 years old
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Life expectancy of at least 12 weeks
Able to swallow and retain oral medications
Incapable of becoming pregnant, or not pregnant and using an adequate form of contraception, i.e. a female who is of:
1. 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);
2. 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) and other acceptable contraceptive methods during the study and continuing for at least 4 weeks after the final dose of treatment with Lapatinib and Capecitabine
Subjects must complete all screening assessments as outlined in the protocol
Subjects must complete the Functional Assessment of Chronic Illness Therapy-Diarrhoea (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
Prior treatment with other chemotherapeutic agents or endocrine therapy is permitted. All prior treatment related toxicities, except diarrhoea and alopecia, must be National Cancer Institute common terminology criteria for adverse events (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
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

Exclusion Criteria:

Concurrent treatment with an investigational agent or concurrent participation in another clinical study
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
Treatment with Octreotide within the 3 months prior to randomization
Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an Epidermal growth factor receptor (EGFR) and/or HER2 inhibitor), or hormonal therapy for treatment of cancer
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)
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
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
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
Pregnant or lactating subjects
Prior treatment with Lapatinib
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

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Olomouc		775 20	Czechia
Novartis Investigative Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 11, 2015	Oct 19, 2018

Arm/Group Information

ID	Title	Description
BG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
BG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks)

Proportion of subjects experiencing at least one episode of diarrhoea with a severity of Grade 2 and above, as defined by the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 4.03, recorded as AEs in the Electronic case report form (eCRF)

ITT - For cycle 1-3 analysis: Subjects that withdrew from the study on or prior to the Cycle 4 visit date were assumed to have experienced diarrhoea. For the cycle 1-8 analysis: Subjects who did not have diarrhea event prior to the End of Study/Withdrawal visit date were not assumed to have experienced diarrhoea.

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Units	Counts
Participants	OG00030 OG00132

Title

Denominators

Categories

Cyclce 1-3 (up to 9 weeks)with impuation

Title	Measurements
	OG0007 OG0019

Cyclce 1-8 (up to 24 weeks)without imputation

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Cycle 1-3 (up to 9 weeks)	Chi-squared		0.775		Difference in Percentages	-4.8			2-Sided	95	-29.2	20.0					Superiority

Secondary

Proportion of Subjects Experiencing Diarrhoea of Grade 3 and Above (up to 24 Weeks)

Proportion of subjects experiencing diarrhoea with a severity of Grade 3 and above, as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Experiencing Diarrhoea of Any Grade of Severity (up to 24 Weeks)

Proportion of subjects experiencing diarrhoea of any grade of severity as defined by the NCI CTCAE, version 4.03 and recorded as AEs in the eCRF

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Duration of Diarrhoea of Any Grade of Severity

Duration of diarrhoea of any grade of severity, recorded as AEs in the eCRF

ITT - including only patients for whom an AE of diarrhoea and its duration was reported

Posted

Mean

Standard Deviation

days

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Time to Onset of the First Episode of Diarrhoea of Any Grade of Severity

Time to onset of the first episode of diarrhoea of any grade of severity, recorded as an AE in the eCRF. Subject are censored if there was no event. Median time and 95% confidence intervals were calculated using Kaplan-Meier estimates.

ITT

Posted

Median

95% Confidence Interval

Days

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Taking Anti-diarrhoeal Medication

Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Who Had Unscheduled Visits to Healthcare Professionals Due to Diarrhoea

Proportion of subjects making diarrhoea related unscheduled visits to healthcare professionals as recorded in the eCRF

ITT - The information to calculate the proportions was not captured in the database.

Posted

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Requiring Dose Reduction in Lapatinib and Capecitabine

Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose reduction as recorded in the eCRF

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Requiring Dose Delay in Lapatinib and Capecitabine

Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose delay as recorded in the eCRF

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Requiring Treatment Withdrawal in Lapatinib and Capecitabine

Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine treatment withdrawal as recorded in the eCRF

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Requiring Use of Diarrhoea-related Intravenous Fluids

Proportion of subjects requiring use of diarrhoea-related intravenous fluids for rehydration as recorded in the eCRF

ITT - The information to calculate the proportions was not captured in the database.

Posted

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Number of Lapatinib and Capecitabine Tablets Dispensed and Returned

Number of Lapatinib and Capecitabine tablets dispensed and returned as recorded in the eCRF

ITT

Posted

Mean

Standard Deviation

tablets

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Overall Response Rate (up to 24 Weeks)

Overall response rate as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >=20% and >= 5mm increase in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Clinical Benefit Response (up to 24 Weeks)

Clinical benefit response as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Clinical Benefit Response rate (CBR) is defined as the percentage of subjects with a CR, PR or SD at week 24.

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Reporting Changes in Bowel Movements From Baseline (Frequency and/or Consistency) as Recorded in the Diarrhoea Management Diary (DMD)

All subjects completed the baseline DMD during the 3 days prior to randomisation, before any study-related treatment is administered. Subjects randomised to receive Octreotide completed a second baseline DMD before starting the first cycle of treatment with Lapatinib and Capecitabine. The baseline DMD comprised of 3 questions to record stool form and consistency. The DMD to be completed throughout the rest of the study comprised of 3 questions in the baseline DMD and a further 5 questions and 6 sub-questions to evaluate the consequences and management of diarrhoea.

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Time to the First Subject Reported Change in Frequency and/or Consistency of Bowel Movements From Baseline as Recorded in the DMD

Event is defined as Subjects reporting change in frequency and/or consistency of bowel movements from baseline at least once in DMD. Subject are censored if there is no change in bowel movement frequency/consistency as compared to baseline. Median time and 95% confidence intervals were calculated using Kaplan-Meier estimates.

ITT

Posted

Median

95% Confidence Interval

Days

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Taking Anti-diarrhoeal Medication as Recorded in the DMD

The proportion of subjects taking medication at least once as a result of diarrhoea are summarised

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Making Dietary Changes Due to Diarrhoea as Recorded in the DMD

The proportion of subjects making dietary changes to help with the diarrhoea are summarised

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Contacting Other Non-hospital Healthcare Professionals to Discuss Diarrhoea as Recorded in the DMD

The proportion of subjects contacting a health care professional other than the hospital doctors/nurses to discuss diarrhoea are summarised

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Secondary

Proportion of Subjects Reporting Stopping Completely or Missing Doses of Anti-cancer Tablets Due to Diarrhoea as Recorded in the DMD

The proportion of subjects reducing or completely stopping the number of anti-cancer tablets to help with diarrhoea are summarised

ITT

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Octreotide Treatment	Subjects randomised to receive Octreotide were administered with Octreotide (Sandostatin LAR™) 40mg 7 days before the start of treatment with Lapatinib and Capecitabine and again 28 days later. All subjects received treatment with Lapatinib 1250milligram (mg) once daily and Capecitabine 1000 milligram/square meter (mg/m^2) twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment. SANDOSTATIN™ is a trademark of Novartis.
OG001	No Octreotide Treatment	Subjects randomised to receive no octreotide, treatment with Lapatinib and Capecitabine was initiated immediately following enrolment. All subjects received treatment with Lapatinib 1250mg once daily and Capecitabine 1000mg/m^2 twice daily until disease progression. Lapatinib was given every day; Capecitabine was given in 3 week cycles of two weeks treatment followed by one week off treatment

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0010 affected33 at risk EG0021 affected62 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0010 affected33 at risk EG0021 affected62 at risk
Vulvitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0010 affected33 at risk EG0021 affected62 at risk
Alanine aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0010 affected33 at risk EG0021 affected62 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0011 affected33 at risk EG0021 affected62 at risk
Paraparesis	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0011 affected33 at risk EG0021 affected62 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0011 affected33 at risk EG0021 affected62 at risk
Thrombosis	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0010 affected33 at risk EG0021 affected62 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0016 affected33 at risk EG0027 affected62 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0014 affected33 at risk EG0025 affected62 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected29 at risk EG0013 affected33 at risk EG0026 affected62 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0010 affected33 at risk EG0022 affected62 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG00017 affected29 at risk EG00115 affected33 at risk EG00232 affected62 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0011 affected33 at risk EG0023 affected62 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0012 affected33 at risk EG0022 affected62 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0012 affected33 at risk EG0024 affected62 at risk
Oral pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0012 affected33 at risk EG0022 affected62 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0012 affected33 at risk EG0024 affected62 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0011 affected33 at risk EG0023 affected62 at risk
Asthenia	General disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0017 affected33 at risk EG0029 affected62 at risk
Fatigue	General disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected29 at risk EG0011 affected33 at risk EG0024 affected62 at risk
Oedema peripheral	General disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0010 affected33 at risk EG0022 affected62 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0012 affected33 at risk EG0024 affected62 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 affected29 at risk EG0011 affected33 at risk EG0024 affected62 at risk
Oral candidiasis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0010 affected33 at risk EG0022 affected62 at risk
Paronychia	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0012 affected33 at risk EG0024 affected62 at risk
Alanine aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0004 affected29 at risk EG0012 affected33 at risk EG0026 affected62 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0004 affected29 at risk EG0011 affected33 at risk EG0025 affected62 at risk
Bilirubin conjugated increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0010 affected33 at risk EG0022 affected62 at risk
Blood bilirubin increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0004 affected29 at risk EG0013 affected33 at risk EG0027 affected62 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0012 affected33 at risk EG0023 affected62 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0012 affected33 at risk EG0022 affected62 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0012 affected33 at risk EG0024 affected62 at risk
Insomnia	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0012 affected33 at risk EG0022 affected62 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0013 affected33 at risk EG0025 affected62 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected29 at risk EG0012 affected33 at risk EG0022 affected62 at risk
Blister	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0010 affected33 at risk EG0022 affected62 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG00013 affected29 at risk EG00111 affected33 at risk EG00224 affected62 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0004 affected29 at risk EG0017 affected33 at risk EG00211 affected62 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected29 at risk EG0012 affected33 at risk EG0024 affected62 at risk
Lymphoedema	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected29 at risk EG0012 affected33 at risk EG0023 affected62 at risk

ID	Term
D009369	Neoplasms
D003967	Diarrhea
D001943	Breast Neoplasms

ID	Term
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D009371	Neoplasms by Site
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D005472	Fluorouracil
D014498	Uracil
D011744	Pyrimidinones
D003853	Deoxyribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D010456	Peptides, Cyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Octreotide Treatment	Octreotide+Lap+Cap	1	29	5	29	26	29
EG001	No Octreotide Treatment	Lap+Cap	0	33	3	33	27	33
EG002	All Patients	All Patients	1	62	8	62	53	62