E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diarrhoea associated with treatment with lapatinib and capecitabine for metastatic breast cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Diarrhoea associated with treatment with lapatinib and capecitabine for metastatic breast cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy of prophylactic octreotide in reducing the proportion of subjects experiencing diarrhoea with a severity of NCI CTCAE Grade 2 and above. |
|
E.2.2 | Secondary objectives of the trial |
Determine the efficacy of prophylactic octreotide (Oct.) in reducing the:
-proportion of subjects experiencing diarrhoea with a severity of NCI CTCAE Grade 3 and above
-proportion of subjects experiencing diarrhoea of any grade of severity
-duration of diarrhoea of any grade of severity
-proportion of subjects taking antidiarrhoeal medication
-proportion of subjects making unscheduled visits to healthcare professionals as a result of diarrhoea
-proportion of subjects requiring changes in cancer therapy as a result of diarrhoea
-proportion of subjects requiring treatment with intravenous fluids resulting from diarrhoea
To determine the efficacy of prophylactic Oct. in reducing the increasing the time to onset of the first episode of diarrhoea of any grade of severity
Determine the efficacy of prophylactic Oct.on:
-compliance with lapatinib and capecitabine treatment
-the efficacy of treatment with lapatinib and capecitabine
-the safety and tolerability of cancer treatment
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Deviations from the inclusion criteria are not allowed because they can potentially
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.
Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Signed written informed consent.
2. Histologically or cytologically confirmed HER2-positive advanced or metastatic
breast cancer which has progressed following prior therapy, which must have
included anthracyclines and taxanes and therapy with trastuzumab in the
metastatic setting.
3. Females age >or=18 years old.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 4)
5. Life expectancy of at least 12 weeks.
6. Able to swallow and retain oral medications.
7. Incapable of becoming pregnant, or not pregnant and using an adequate form of
contraception, i.e. a female who is of:
a. non-childbearing potential (physiologically incapable of becoming pregnant), including any female who has had hysterectomy, bilateral
oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for at least 1 year);
b. childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment with octreotide if randomised to receive octreotide or the first dose of lapatinib with capecitabine if randomised to receive no
octreotide, preferably as close to the first dose as possible, and must agree to use adequate contraception (intrauterine device, birth control pills unless clinically contraindicated, or barrier device) during the study and continuing for at least 4 weeks after the final dose of treatment with lapatinib and capecitabine.
8. Subjects must complete all screening assessments as outlined in the protocol.
9. Subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of octreotide if randomised to receive octreotide. All subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of lapatinib with capecitabine.
10. Prior treatment with other chemotherapeutic agents or endocrine therapy is permitted. All prior treatment related toxicities, except diarrhoea and alopecia,
must be NCI CTCAE (version 4.03) ≤ Grade 1 at the time of randomization.
Subjects with diarrhoea with any grade of severity within 14 days prior to randomisation are excluded from LAP117314.
11. Prior treatment with radiation therapy is permitted provided that at least 2 weeks
have elapsed since the last fraction of radiation therapy prior to treatment with octreotide if randomised to receive octreotide or the first dose of lapatinib with capecitabine if randomised to receive no octreotide, and all radiation therapy related AEs are ≤ Grade 1 at the time of randomization.
French subjects: In France, a subject will be eligible for inclusion in this study only if
either affiliated to or a beneficiary of a social security category. Other country-specific
criteria are included in Appendix 5. |
|
E.4 | Principal exclusion criteria |
Deviations from exclusion criteria are not allowed because they can potentially
jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.
Therefore, adherence to the criteria as specified in the protocol is essential.
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Concurrent treatment with an investigational agent or concurrent participation in another clinical study.
2. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to treatment with octreotide for subjects randomised to receive octreotide or the first dose of lapatinib and capecitabine for subjects randomised to receive no octreotide.
3. Treatment with octreotide within the 3 months prior to randomization.
4. Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy
(including an EGFR and/or HER2 inhibitor), or hormonal therapy for treatment of cancer.
5. Dementia, altered mental status, or any psychiatric condition that would prohibit
the understanding or rendering of informed consent, unless a legally acceptable
representative could provide informed consent (if in accordance with the policies of the local Ethics Committee).
6. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety or compliance with study procedures.
7. Diarrhoea with any grade of severity within 14 days prior to treatment with
octreotide for subjects randomised to receive octreotide or within 14 days prior to the first dose of lapatinib and capecitabine for subjects randomised to receive no octreotide.
8. Malabsorption syndrome, inflammatory bowel disease (ulcerative colitis,
Chrohn’s disease), irritable bowel syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
9. Pregnant or lactating subjects.
French subjects: the French subject has participated in any study using an
investigational drug during the previous 30 days or 5 half-lives, whichever is longer,
preceding the first dose of protocol treatment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects experiencing diarrhoea with a severity of Grade 2 and above, as defined by the NCI CTCAE, version 4.03. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluated following 24 weeks of treatment with lapatinib and capecitabine |
|
E.5.2 | Secondary end point(s) |
Investigator Reported
•Proportion of subjects experiencing diarrhoea with a severity of Grade 3 and above, as defined by the NCI CTCAE, version 4.03, recorded as AEs in the eCRF.
•Proportion of subjects experiencing diarrhoea of any grade of severity as defined by the NCI CTCAE, version 4.03, recorded as AEs in the eCRF.
•Duration of diarrhoea of any grade of severity, recorded as AEs in the eCRF.
•Time to onset of the first episode of diarrhoea of any grade of severity, recorded as an AE in the eCRF.
•Proportion of subjects taking anti-diarrhoeal medication, recorded in the eCRF.
•Proportion of subjects making diarrhoea-related unscheduled visits to healthcare professionals, recorded in the eCRF.
•Proportion of subjects requiring diarrhoea-related lapatinib and capecitabine dose reduction, dose delay and treatment withdrawal, recorded in the eCRF.
•Proportion of subjects requiring use of diarrhoea-related intravenous fluids for rehydration, recorded in the eCRF.
•Number of lapatinib and capecitabine tablets dispensed and returned, recorded in the eCRF.
•Overall response rate and clinical benefit response measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.
•Proportion of subjects with AEs and SAEs, recorded in the eCRF.
Subject Reported
•Proportion of subjects experiencing diarrhoea of any grade of severity, recorded in the diarrhoea diary.
•Time to onset of the first episode of diarrhoea of any grade of severity, recorded in the diarrhoea diary.
•Proportion of subjects taking anti-diarrhoeal medication, recorded in the diarrhoea diary.
•Proportion of subjects making dietary changes due to diarrhoea, recorded in the diarrhoea diary.
•Proportion of subjects making unscheduled visits to healthcare professionals due to diarrhoea, recorded in the diarrhoea diary.
•Proportion of subjects missing doses of lapatinib and capecitabine due to diarrhoea, recorded in the diarrhoea diary.
Quality of Life
•Proportion of subjects with improvement in quality of life, recorded by FACIT-D.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluated following 24 weeks of treatment with lapatinib and capecitabine |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Hong Kong |
Israel |
Russian Federation |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
A subject will be considered to have completed the study if the subject completes 24 weeks of treatment with lapatinib and capecitabine, or if cancer progresses or the subject dies during treatment, whichever is sooner. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |