Clinical Trials /

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

NCT02294786

Description:

Diarrhoea is the most commonly reported adverse events (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 will evaluate 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 will be 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 will be randomized out of which 70 will receive octreotide and 70 will receive no Octreotide

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 117314
  • NCT ID: NCT02294786

Conditions

  • Cancer

Interventions

DrugSynonymsArms
LapatinibNo Octreotide treatment
CapecitabineNo Octreotide treatment
OctreotideOctreotide treatment

Purpose

Diarrhoea is the most commonly reported adverse events (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 will evaluate 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 will be 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 will be randomized out of which 70 will receive octreotide and 70 will receive no Octreotide

Trial Arms

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

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

          -  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

          -  Prior treatment with Lapatinib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of Subjects experiencing diarrhoea of Grade 2 and above
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects experiencing 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

Measure:Proportion of subjects experiencing diarrhoea of Grade 3 and above
Time Frame:Up to 24 weeks
Safety Issue:
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
Measure:Proportion of subjects experiencing diarrhoea of any grade of severity
Time Frame:Up to 24 weeks
Safety Issue:
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
Measure:Duration of diarrhoea of any grade of severity
Time Frame:Up to 24 weeks
Safety Issue:
Description:Duration of diarrhoea of any grade of severity, recorded as AEs in the eCRF
Measure:Time to onset of the first episode of diarrhoea of any grade of severity
Time Frame:Up to 24 weeks
Safety Issue:
Description:Time to onset of the first episode of diarrhoea of any grade of severity, recorded as an AE in the eCRF
Measure:Proportion of subjects taking anti-diarrhoeal medication
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects taking anti-diarrhoeal medication as recorded in the eCRF
Measure:Proportion of subjects who had unscheduled visits to healthcare professionals due to diarrhoea
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects making diarrhoea related unscheduled visits to healthcare professionals as recorded in the eCRF
Measure:Proportion of subjects requiring dose reduction in Lapatinib and Capecitabine
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose reduction as recorded in the eCRF
Measure:Proportion of subjects requiring dose delay in Lapatinib and Capecitabine
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine dose delay as recorded in the eCRF
Measure:Proportion of subjects requiring treatment withdrawal in Lapatinib and Capecitabine
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects requiring diarrhoea related Lapatinib and Capecitabine treatment withdrawal as recorded in the eCRF
Measure:Proportion of subjects requiring use of diarrhoea-related intravenous fluids
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects requiring use of diarrhoea-related intravenous fluids for rehydration as recorded in the eCRF
Measure:Number of Lapatinib and Capecitabine tablets dispensed and returned
Time Frame:Up to 24 weeks
Safety Issue:
Description:Number of Lapatinib and Capecitabine tablets dispensed and returned as recorded in the eCRF
Measure:Overall Response Rate
Time Frame:Up to 24 weeks
Safety Issue:
Description:Overall response rate as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measure:Clinical Benefit Response
Time Frame:Up to 24 weeks
Safety Issue:
Description:Clinical benefit response as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
Measure:Proportion of subjects with AEs and SAEs
Time Frame:Up to 24 weeks
Safety Issue:
Description:Proportion of subjects with AEs and SAEs were assessed from the start of the study until end of study as recorded in the eCRF
Measure:Proportion of subjects reporting changes in bowel movements from baseline (frequency and/or consistency) as recorded in the Diarrhoea Management Diary (DMD)
Time Frame:Up to 24 weeks
Safety Issue:
Description:All subjects will complete the baseline DMD during the 3 days prior to randomisation, before any study-related treatment is administered. Subjects randomised to receive Octreotide will complete a second baseline DMD before starting the first cycle of treatment with Lapatinib and Capecitabine. The baseline DMD will comprise of 3 questions to record stool form and consistency. The DMD to be completed throughout the rest of the study will comprise of 3 questions in the baseline DMD and a further 5 questions and 6 sub-questions to evaluate the consequences and management of diarrhoea
Measure:Time to the first subject reported change in frequency and/or consistency of bowel movements from baseline as recorded in the DMD
Time Frame:Up to 24 weeks
Safety Issue:
Description:The time to onset of the first subject-reported increase in frequency and/or worsening of consistency of bowel movements will be summarised by treatment arm
Measure:Proportion of subjects taking anti-diarrhoeal medication as recorded in the DMD
Time Frame:Up to 24 weeks
Safety Issue:
Description:The proportion of subjects taking medication at least once as a result of diarrhoea will be summarised and analysed
Measure:Proportion of subjects making dietary changes due to diarrhoea as recorded in the DMD
Time Frame:Up to 24 weeks
Safety Issue:
Description:The proportion of subjects making dietary changes to help with the diarrhoea will be summarised and analysed using the Generalised Estimating Equations (GEE) analysis and plots
Measure:Proportion of subjects contacting other non-hospital healthcare professionals to discuss diarrhoea as recorded in the DMD
Time Frame:Up to 24 weeks
Safety Issue:
Description:The proportion of subjects contacting a health care professional other than the hospital doctors/nurses to discuss diarrhoea will be summarised and analysed using the GEE analysis and plots
Measure:Proportion of subjects reporting stopping completely or missing doses of anti-cancer tablets due to diarrhoea as recorded in the DMD
Time Frame:Up to 24 weeks
Safety Issue:
Description:The proportion of subjects reducing or completely stopping the number of anti-cancer tablets to help with diarrhoea will be summarised and analysed using the GEE analysis and plots. Summaries will be performed separately for each type of change in anti-cancer tablets (i.e. reducing tablets and stopping completely) as well as overall

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Randomised
  • Octreotide
  • Diarrhoea
  • Phase II
  • Capecitabine
  • Quality of life
  • Metastatic breast cancer
  • HER2
  • Lapatinib
  • Diarrhoea diary

Last Updated

December 5, 2017