Diarrhoea associated with treatment with lapatinib and capecitabine for metastatic breast cancer MedDRA version: 18.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Sandostatin® LAR®
Pharmaceutical Form:
INN or Proposed INN: Octerotide
CAS Number: 79517-01-4
Other descriptive name: OCTREOTIDE ACETATE
Concentration unit: mg milligram(s)
Concentration
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Deviations from the inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Signed written informed consent. 2. Histologically or cytologically confirmed HER2-positive advanced or metastatic breast cancer which has progressed following prior therapy, which must have included anthracyclines and taxanes and therapy with trastuzumab in the metastatic setting. 3. Females age >or=18 years old. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 4) 5. Life expectancy of at least 12 weeks. 6. Able to swallow and retain oral medications. 7. Incapable of becoming pregnant, or not pregnant and using an adequate form of contraception, i.e. a female who is of: a. non-childbearing potential (physiologically incapable of becoming pregnant), including any female who has had hysterectomy, bilateral oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for at least 1 year); b. childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment with octreotide if randomised to receive octreotide or the first dose of lapatinib with capecitabine if randomised to receive no octreotide, preferably as close to the first dose as possible, and must agree to use adequate contraception (intrauterine device, birth control pills unless clinically contraindicated, or barrier device) during the study and continuing for at least 4 weeks after the final dose of treatment with lapatinib and capecitabine. Acceptable contraceptive methods are described in Section 7.5.1 8. Subjects must complete all screening assessments as outlined in the protocol. 9. Subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of octreotide if randomised to receive octreotide. All subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of lapatinib with capecitabine. 10. Prior treatment with other chemotherapeutic agents or endocrine therapy is permitted. All prior treatment related toxicities, except diarrhoea and alopecia, must be NCI CTCAE (version 4.03) = Grade 1 at the time of randomization. Subjects with diarrhoea with any grade of severity within 14 days prior to randomisation are excluded from LAP117314. 11. Prior treatment with radiation therapy is permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy prior to treatment with octreotide if randomised to receive octreotide or the first dose of lapatinib with capecitabine if randomised to receive no octreotide, and all radiation therapy related AEs are = Grade 1 at the time of randomization. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Other country-specific criteria are included in Appendix 5. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 98
Exclusion criteria
Exclusion criteria: Deviations from exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. Subjects meeting any of the following criteria must not be enrolled in the study: 1. Concurrent treatment with an investigational agent or concurrent participation in another clinical study. 2. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to treatment with octreotide for subjects randomised to receive octreotide or the first dose of lapatinib and capecitabine for subjects randomised to receive no octreotide. 3. Treatment with octreotide within the 3 months prior to randomization. 4. Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an EGFR and/or HER2 inhibitor), or hormonal therapy for treatment of cancer. 5. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent, unless a legally acceptable representative could provide informed consent (if in accordance with the policies of the local Ethics Committee). 6. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety or compliance with study procedures. 7. Diarrhoea with any grade of severity within 14 days prior to treatment with octreotide for subjects randomised to receive octreotide or within 14 days prior to the first dose of lapatinib and capecitabine for subjects randomised to receive no octreotide. 8. Malabsorption syndrome, inflammatory bowel disease (ulcerative colitis, Chrohn’s disease), irritable bowel syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. 9. Pregnant or lactating subjects. 10. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of prophylactic octreotide in reducing the proportion of subjects experiencing diarrhoea with a severity of NCI CTCAE Grade 2 and above.;Secondary Objective: Determine the efficacy of prophylactic octreotide (Oct.) in reducing the: -proportion of subjects experiencing diarrhoea with a severity of NCI CTCAE Grade 3 and above -proportion of subjects experiencing diarrhoea of any grade of severity -duration of diarrhoea of any grade of severity -proportion of subjects taking antidiarrhoeal medication -proportion of subjects making unscheduled visits to healthcare professionals as a result of diarrhoea -proportion of subjects requiring changes in cancer therapy as a result of diarrhoea -proportion of subjects requiring treatment with intravenous fluids resulting from diarrhoea To determine the efficacy of prophylactic Oct. in reducing the increasing the time to onset of the first episode of diarrhoea of any grade of severity Determine the efficacy of prophylactic Oct.on: -compliance with lapatinib and capecitabine treatment -the efficacy of treatment with lapatinib and capecitabine -the safety and tolerability of cancer treatment ;Primary end point(s): Proportion of subjects experiencing diarrhoea with a severity of Grade 2 and above, as defined by the NCI CTCAE, version 4.03., recorded as AEs in the eCRF.;Timepoint(s) of evaluation of this end point: Evaluated following 24 weeks of treatment with lapatinib and capecitabine | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Investigator Reported (eCRF) •Proportion of subjects experiencing diarrhoea with a severity of Grade 3 and above, as defined by the NCI CTCAE, version 4.03, recorded as AEs in the eCRF. •Proportion of subjects experiencing diarrhoea of any grade of severity as defined by the NCI CTCAE, version 4.03, recorded as AEs in the eCRF. •Duration of diarrhoea of any grade of severity, recorded as AEs in the eCRF. •Time to onset of the first episode of diarrhoea of any grade of severity, recorded as an AE in the eCRF. •Proportion of subjects taking anti-diarrhoeal medication, recorded in the eCRF. •Proportion of subjects making diarrhoea-related unscheduled visits to healthcare professionals, recorded in the eCRF. •Proportion of subjects requiring diarrhoea-related lapatinib and capecitabine dose reduction, dose delay and treatment withdrawal, recorded in the eCRF. •Proportion of subjects requiring use of diarrhoea-related intravenous fluids for rehydration, recorded in the eCRF. •Number of lapatinib and capecitabine tablets dispensed and returned, recorded in the eCRF. •Overall response rate and clinical benefit response measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. •Proportion of subjects with AEs and SAEs, recorded in the eCRF. Patient Reported (DMD) •Proportion of patients reporting changes in bowel movements from baseline (frequency and/or consistency) recorded in the DMD. •Time to onset of the first patient reported change in frequency and/or consistency of bowel movements from baseline recorded in the DMD. •Proportion of patientstaking anti-diarrhoeal medication recorded in the DMD. •Proportion of patients making dietary changes due to diarrhoea recorded in the DMD. •Proportion of patients contacting other non-hospital healthcare professionals to discuss diarrhoea, recorded in the DMD. •Proportion of patients reporting stopping completely or missing doses of anti-cancer tab | — |
Countries
Czech Republic, France, Greece, Hong Kong, Israel, Italy, Poland, Russian Federation, United Kingdom
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed