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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02294786
• Collaborator: (none)
• Enrollment: 62
• Locations: 17
• Arms: 2
• Actual Duration (Months): 34.1
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Diarrhoea is the most commonly reported adverse event (AE) associated with Lapatinib treatment, and is also commonly associated with Capecitabine treatment. Although these events are generally mild to moderate in severity, diarrhoea adversely affects the tolerability of cancer treatment, and in severe cases diarrhoea has the potential to affect the efficacy of treatment due to poor compliance, or treatment interruption or withdrawal. The efficacy of Octreotide in the management of cancer treatment-associated diarrhoea has not been extensively evaluated in large, well-controlled studies. This is a randomised, multi-centre, open-label Phase II study in subjects with Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer which has progressed following prior therapy, which must have included anthracyclines and taxanes and therapy with Trastuzumab in the metastatic setting. This study is not placebo controlled, and there is no active comparator. The study evaluates whether the prophylactic use of Octreotide Long Acting Release (LAR) offers a clinically meaningful benefit by reducing the frequency and severity of diarrhoea associated with treatment with Lapatinib and Capecitabine. Study completion for a subject is defined as the completion of 24 weeks of treatment with Lapatinib and Capecitabine, or progression of cancer or the death of the subject during treatment, whichever occurs first. Approximately 140 subjects were planned to be randomized out of which 70 were planned to receive octreotide and 70 were planned to receive no Octreotide.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: Lapatinib; Drug: Capecitabine; Drug: Octreotide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Dec 17, 2014
• Actual Primary Completion Date: Oct 19, 2017
• Actual Study Completion Date: Oct 19, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Lapatinib; 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; Drug: Capecitabine; Capecitabine (Xeloda™) was supplied as a biconvex, oblong, light peach or peach colored film-coated tablet for oral administration. Each light peach colored tablet contained 150mg Capecitabine and each peach colored tablet contained 500mg Capecitabine. Generic versions of capecitabine may have been used within the study if Xeloda cannot be provided. XELODA™ is a trademark of Hoffmann-La Roche AG.; Drug: Octreotide; Octreotide (Sandostatin LAR™) was supplied as sterile 5milliliter (mL) vials delivering 20mg Octreotide as the free peptide. When mixed with diluent (approximately 2mL or 2.5 mL) it becomes a suspension that is given as an intramuscular injection. Two 20mg intramuscular injections were given to deliver a total dose of 40mg. The Octreotide is uniformly distributed within the microspheres which are made of a biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer. Sterile mannitol was added to the microspheres to improve suspendability
Experimental: 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	Drug: Lapatinib; 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; Drug: Capecitabine; Capecitabine (Xeloda™) was supplied as a biconvex, oblong, light peach or peach colored film-coated tablet for oral administration. Each light peach colored tablet contained 150mg Capecitabine and each peach colored tablet contained 500mg Capecitabine. Generic versions of capecitabine may have been used within the study if Xeloda cannot be provided. XELODA™ is a trademark of Hoffmann-La Roche AG.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

3. Duration of Diarrhoea of Any Grade of Severity [Up to 24 weeks]

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

4. Time to Onset of the First Episode of Diarrhoea of Any Grade of Severity [Up to 24 weeks]

   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.

5. Proportion of Subjects Taking Anti-diarrhoeal Medication [Up to 24 weeks]

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

6. Proportion of Subjects Who Had Unscheduled Visits to Healthcare Professionals Due to Diarrhoea [Up to 24 weeks]

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

7. Proportion of Subjects Requiring Dose Reduction in Lapatinib and Capecitabine [Up to 24 weeks]

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

8. Proportion of Subjects Requiring Dose Delay in Lapatinib and Capecitabine [Up to 24 weeks]

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

9. Proportion of Subjects Requiring Treatment Withdrawal in Lapatinib and Capecitabine [Up to 24 weeks]

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

10. Proportion of Subjects Requiring Use of Diarrhoea-related Intravenous Fluids [Up to 24 weeks]

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

11. Number of Lapatinib and Capecitabine Tablets Dispensed and Returned [Up to 24 weeks]

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

12. Overall Response Rate (up to 24 Weeks) [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.

13. Clinical Benefit Response (up to 24 Weeks) [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.

14. Proportion of Subjects Reporting Changes in Bowel Movements From Baseline (Frequency and/or Consistency) as Recorded in the Diarrhoea Management Diary (DMD) [Up to 24 weeks]

    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.

15. Time to the First Subject Reported Change in Frequency and/or Consistency of Bowel Movements From Baseline as Recorded in the DMD [Up to 24 weeks]

    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.

16. Proportion of Subjects Taking Anti-diarrhoeal Medication as Recorded in the DMD [Up to 24 weeks]

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

17. Proportion of Subjects Making Dietary Changes Due to Diarrhoea as Recorded in the DMD [Up to 24 weeks]

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

18. Proportion of Subjects Contacting Other Non-hospital Healthcare Professionals to Discuss Diarrhoea as Recorded in the DMD [Up to 24 weeks]

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

19. Proportion of Subjects Reporting Stopping Completely or Missing Doses of Anti-cancer Tablets Due to Diarrhoea as Recorded in the DMD [Up to 24 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Olomouc		Czechia	775 20
2	Novartis Investigative Site	Tel Aviv		Israel	69710
3	Novartis Investigative Site	Gdansk		Poland	80-219
4	Novartis Investigative Site	Konin		Poland	62-500
5	Novartis Investigative Site	Warszawa		Poland	01-748
6	Novartis Investigative Site	Khanty mansiysk		Russian Federation	628012
7	Novartis Investigative Site	Moscow		Russian Federation	125367
8	Novartis Investigative Site	Nizhniy Novgorod		Russian Federation	603081
9	Novartis Investigative Site	Obninsk		Russian Federation	249036
10	Novartis Investigative Site	St. Petersburg		Russian Federation	197022
11	Novartis Investigative Site	St. Petersburg		Russian Federation	197758
12	Novartis Investigative Site	St. Petersburg		Russian Federation	198255
13	Novartis Investigative Site	Tomsk		Russian Federation	634050
14	Novartis Investigative Site	London		United Kingdom	SE5 9RS
15	Novartis Investigative Site	Nottingham		United Kingdom	NG5 1PB
16	Novartis Investigative Site	Plymouth		United Kingdom	PL6 8DH
17	Novartis Investigative Site	Romford		United Kingdom	RM7 0AG

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Sep 11, 2015
• Statistical Analysis Plan - Nov 28, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02294786
• Other Study ID Numbers: 117314
• First Posted: Nov 19, 2014
• Last Update Posted: Jul 15, 2019
• Last Verified: May 1, 2019

• Keywords provided by Novartis Pharmaceuticals: Randomised; Octreotide; Diarrhoea; Phase II; Capecitabine; Quality of life; Metastatic breast cancer; HER2; Lapatinib; Diarrhoea diary
• Additional relevant MeSH terms: Diarrhea; Capecitabine; Lapatinib; Octreotide

Study Results

Participant Flow

Recruitment Details	The study enrolled 62 women in 17 centers; Czech Republic (1), Israel (1), Poland (3), the United Kingdom (4) Russian Federation (8)
Pre-assignment Detail	The study was terminated early after 62 patients (out of 140 planned) were randomized as criteria for futility was met.

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Period Title: Overall Study
STARTED	30	32
Safety Population	29	33
ITT Population	30	32
COMPLETED	19	18
NOT COMPLETED	11	14

Baseline Characteristics

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment	Total
Arm/Group Description	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.	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	Total of all reporting groups
Overall Participants	30	32	62
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.4 (10.07)	55.9 (9.08)	56.6 (9.52)
Sex: Female, Male (Count of Participants)
Female	30 100%	32 100%	62 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	0 0%	1 3.1%	1 1.6%
Not Hispanic or Latino	30 100%	31 96.9%	61 98.4%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks)
Description	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)
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Cyclce 1-3 (up to 9 weeks)with impuation	7 23.3%	9 28.1%
Cyclce 1-8 (up to 24 weeks)without imputation	6 20%	5 15.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Octreotide Treatment, No Octreotide Treatment
	Comments	Cycle 1-3 (up to 9 weeks)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.775
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -29.2 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Subjects Experiencing Diarrhoea of Grade 3 and Above (up to 24 Weeks)
Description	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
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	2 6.7%	0 0%

3. Secondary Outcome

Title	Proportion of Subjects Experiencing Diarrhoea of Any Grade of Severity (up to 24 Weeks)
Description	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
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	18 60%	14 43.8%

4. Secondary Outcome

Title	Duration of Diarrhoea of Any Grade of Severity
Description	Duration of diarrhoea of any grade of severity, recorded as AEs in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	17	13
Mean (Standard Deviation) [days]	8.7 (11.15)	36.8 (48.59)

5. Secondary Outcome

Title	Time to Onset of the First Episode of Diarrhoea of Any Grade of Severity
Description	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.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Median (95% Confidence Interval) [Days]	NA	170

6. Secondary Outcome

Title	Proportion of Subjects Taking Anti-diarrhoeal Medication
Description	Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	7 23.3%	11 34.4%

7. Secondary Outcome

Title	Proportion of Subjects Who Had Unscheduled Visits to Healthcare Professionals Due to Diarrhoea
Description	Proportion of subjects making diarrhoea related unscheduled visits to healthcare professionals as recorded in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	0	0

8. Secondary Outcome

Title	Proportion of Subjects Requiring Dose Reduction in Lapatinib and Capecitabine
Description	Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose reduction as recorded in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Subjects requiring dose reduction in Lapatinib	1 3.3%	0 0%
Subjects requiring dose reduction in Capecitabine	1 3.3%	2 6.3%

9. Secondary Outcome

Title	Proportion of Subjects Requiring Dose Delay in Lapatinib and Capecitabine
Description	Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose delay as recorded in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Subjects requiring dose delay in Lapatinib	2 6.7%	2 6.3%
Subjects requiring dose delay in Capecitabine	2 6.7%	2 6.3%

10. Secondary Outcome

Title	Proportion of Subjects Requiring Treatment Withdrawal in Lapatinib and Capecitabine
Description	Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine treatment withdrawal as recorded in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Requiring treatment withdrawal in Lapatinib	0 0%	0 0%
Requiring treatment withdrawal in Capecitabine	0 0%	0 0%

11. Secondary Outcome

Title	Proportion of Subjects Requiring Use of Diarrhoea-related Intravenous Fluids
Description	Proportion of subjects requiring use of diarrhoea-related intravenous fluids for rehydration as recorded in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	0	0

12. Secondary Outcome

Title	Number of Lapatinib and Capecitabine Tablets Dispensed and Returned
Description	Number of Lapatinib and Capecitabine tablets dispensed and returned as recorded in the eCRF
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Number of Lapatinib tablets dispensed	1197.5 (403.12)	1115.6 (495.9)
Number of Lapatinib tablets returned	477.1 (173.94)	403.3 (238.47)
Number of Capecitabine tablets dispensed	1022.6 (473.44)	1011.2 (532.06)
Number of Capecitabine tablets returned	186.1 (157.19)	210 (196.64)

13. Secondary Outcome

Title	Overall Response Rate (up to 24 Weeks)
Description	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.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
complete response (CR)	0 0%	2 6.3%
partial response (PR)	6 20%	4 12.5%
stable disease (SD)	4 13.3%	5 15.6%
Progressive Disease	14 46.7%	17 53.1%
Not Evaluable	6 20%	4 12.5%

14. Secondary Outcome

Title	Clinical Benefit Response (up to 24 Weeks)
Description	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.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	7 23.3%	9 28.1%

15. Secondary Outcome

Title	Proportion of Subjects Reporting Changes in Bowel Movements From Baseline (Frequency and/or Consistency) as Recorded in the Diarrhoea Management Diary (DMD)
Description	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.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	23 76.7%	29 90.6%

16. Secondary Outcome

Title	Time to the First Subject Reported Change in Frequency and/or Consistency of Bowel Movements From Baseline as Recorded in the DMD
Description	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.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Median (95% Confidence Interval) [Days]	22.0	8.0

17. Secondary Outcome

Title	Proportion of Subjects Taking Anti-diarrhoeal Medication as Recorded in the DMD
Description	The proportion of subjects taking medication at least once as a result of diarrhoea are summarised
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	2 6.7%	2 6.3%

18. Secondary Outcome

Title	Proportion of Subjects Making Dietary Changes Due to Diarrhoea as Recorded in the DMD
Description	The proportion of subjects making dietary changes to help with the diarrhoea are summarised
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	9 30%	11 34.4%

19. Secondary Outcome

Title	Proportion of Subjects Contacting Other Non-hospital Healthcare Professionals to Discuss Diarrhoea as Recorded in the DMD
Description	The proportion of subjects contacting a health care professional other than the hospital doctors/nurses to discuss diarrhoea are summarised
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	4 13.3%	3 9.4%

20. Secondary Outcome

Title	Proportion of Subjects Reporting Stopping Completely or Missing Doses of Anti-cancer Tablets Due to Diarrhoea as Recorded in the DMD
Description	The proportion of subjects reducing or completely stopping the number of anti-cancer tablets to help with diarrhoea are summarised
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Octreotide Treatment	No Octreotide Treatment
Arm/Group Description	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.	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
Measure Participants	30	32
Count of Participants [Participants]	2 6.7%	3 9.4%

Adverse Events

Time Frame	Up to 28 weeks post randomization (from randomization until up to and including 4 weeks after the last dose of study treatment)
Arm/Group Title	Octreotide Treatment		No Octreotide Treatment		All Patients
Arm/Group Description	Octreotide+Lap+Cap		Lap+Cap		All Patients
All Cause Mortality
	Octreotide Treatment		No Octreotide Treatment		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		0/33 (0%)		1/62 (1.6%)
Serious Adverse Events
	Octreotide Treatment		No Octreotide Treatment		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/29 (17.2%)		3/33 (9.1%)		8/62 (12.9%)
Gastrointestinal disorders
Diarrhoea	1/29 (3.4%)		0/33 (0%)		1/62 (1.6%)
Infections and infestations
Lower respiratory tract infection	1/29 (3.4%)		0/33 (0%)		1/62 (1.6%)
Vulvitis	1/29 (3.4%)		0/33 (0%)		1/62 (1.6%)
Investigations
Alanine aminotransferase increased	1/29 (3.4%)		0/33 (0%)		1/62 (1.6%)
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw	0/29 (0%)		1/33 (3%)		1/62 (1.6%)
Nervous system disorders
Paraparesis	0/29 (0%)		1/33 (3%)		1/62 (1.6%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/29 (0%)		1/33 (3%)		1/62 (1.6%)
Vascular disorders
Thrombosis	1/29 (3.4%)		0/33 (0%)		1/62 (1.6%)
Other (Not Including Serious) Adverse Events
	Octreotide Treatment		No Octreotide Treatment		All Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/29 (89.7%)		27/33 (81.8%)		53/62 (85.5%)
Blood and lymphatic system disorders
Anaemia	1/29 (3.4%)		6/33 (18.2%)		7/62 (11.3%)
Neutropenia	1/29 (3.4%)		4/33 (12.1%)		5/62 (8.1%)
Thrombocytopenia	3/29 (10.3%)		3/33 (9.1%)		6/62 (9.7%)
Gastrointestinal disorders
Abdominal pain	2/29 (6.9%)		0/33 (0%)		2/62 (3.2%)
Diarrhoea	17/29 (58.6%)		15/33 (45.5%)		32/62 (51.6%)
Dry mouth	2/29 (6.9%)		1/33 (3%)		3/62 (4.8%)
Mouth ulceration	0/29 (0%)		2/33 (6.1%)		2/62 (3.2%)
Nausea	2/29 (6.9%)		2/33 (6.1%)		4/62 (6.5%)
Oral pain	0/29 (0%)		2/33 (6.1%)		2/62 (3.2%)
Stomatitis	2/29 (6.9%)		2/33 (6.1%)		4/62 (6.5%)
Vomiting	2/29 (6.9%)		1/33 (3%)		3/62 (4.8%)
General disorders
Asthenia	2/29 (6.9%)		7/33 (21.2%)		9/62 (14.5%)
Fatigue	3/29 (10.3%)		1/33 (3%)		4/62 (6.5%)
Oedema peripheral	2/29 (6.9%)		0/33 (0%)		2/62 (3.2%)
Hepatobiliary disorders
Hyperbilirubinaemia	2/29 (6.9%)		2/33 (6.1%)		4/62 (6.5%)
Infections and infestations
Lower respiratory tract infection	3/29 (10.3%)		1/33 (3%)		4/62 (6.5%)
Oral candidiasis	2/29 (6.9%)		0/33 (0%)		2/62 (3.2%)
Paronychia	2/29 (6.9%)		2/33 (6.1%)		4/62 (6.5%)
Investigations
Alanine aminotransferase increased	4/29 (13.8%)		2/33 (6.1%)		6/62 (9.7%)
Aspartate aminotransferase increased	4/29 (13.8%)		1/33 (3%)		5/62 (8.1%)
Bilirubin conjugated increased	2/29 (6.9%)		0/33 (0%)		2/62 (3.2%)
Blood bilirubin increased	4/29 (13.8%)		3/33 (9.1%)		7/62 (11.3%)
Metabolism and nutrition disorders
Decreased appetite	1/29 (3.4%)		2/33 (6.1%)		3/62 (4.8%)
Musculoskeletal and connective tissue disorders
Bone pain	0/29 (0%)		2/33 (6.1%)		2/62 (3.2%)
Pain in extremity	2/29 (6.9%)		2/33 (6.1%)		4/62 (6.5%)
Psychiatric disorders
Insomnia	0/29 (0%)		2/33 (6.1%)		2/62 (3.2%)
Respiratory, thoracic and mediastinal disorders
Cough	2/29 (6.9%)		3/33 (9.1%)		5/62 (8.1%)
Epistaxis	0/29 (0%)		2/33 (6.1%)		2/62 (3.2%)
Skin and subcutaneous tissue disorders
Blister	2/29 (6.9%)		0/33 (0%)		2/62 (3.2%)
Palmar-plantar erythrodysaesthesia syndrome	13/29 (44.8%)		11/33 (33.3%)		24/62 (38.7%)
Rash	4/29 (13.8%)		7/33 (21.2%)		11/62 (17.7%)
Skin fissures	2/29 (6.9%)		2/33 (6.1%)		4/62 (6.5%)
Vascular disorders
Lymphoedema	1/29 (3.4%)		2/33 (6.1%)		3/62 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.