Clinical trial NCT02294786: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cancer
Keywords: Randomised
Octreotide
Diarrhoea
Phase II
Capecitabine
Quality of life
Metastatic breast cancer
HER2
Lapatinib
Diarrhoea diary
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-11-19
Enrollment: 62
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* Histologically or cytologically confirmed HER2-positive advanced or metastatic breast cancer which has progressed following prior therapy, which must have included anthracyclines and taxanes and therapy with trastuzumab in the metastatic setting
* Females age \>=18 years old
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Life expectancy of at least 12 weeks
* Able to swallow and retain oral medications
* Incapable of becoming pregnant, or not pregnant and using an adequate form of contraception, i.e. a female who is of:

  1. non-childbearing potential (physiologically incapable of becoming pregnant), including any female who has had hysterectomy, bilateral oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for at least 1 year);
  2. childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment with Octreotide if randomised to receive Octreotide or the first dose of Lapatinib with Capecitabine if randomised to receive no Octreotide, preferably as close to the first dose as possible, and must agree to use adequate contraception (intrauterine device, birth control pills unless clinically contraindicated, or barrier device) and other acceptable contraceptive methods during the study and continuing for at least 4 weeks after the final dose of treatment with Lapatinib and Capecitabine
* Subjects must complete all screening assessments as outlined in the protocol
* Subjects must complete the Functional Assessment of Chronic Illness Therapy-Diarrhoea (FACIT-D) and diarrhoea diary before receiving the first dose of Octreotide if randomised to receive Octreotide. All subjects must complete the FACIT-D and diarrhoea diary before receiving the first dose of Lapatinib with Capecitabine
* Prior treatment with other chemotherapeutic agents or endocrine therapy is permitted. All prior treatment related toxicities, except diarrhoea and alopecia, must be National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) (version 4.03)\<= Grade 1 at the time of randomization.Subjects with diarrhoea with any grade of severity within 14 days prior to randomisation are excluded from LAP117314
* Prior treatment with radiation therapy is permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy prior to treatment with Octreotide if randomised to receive Octreotide or the first dose of Lapatinib with Capecitabine if randomised to receive no Octreotide, and all radiation therapy related AEs are \<= Grade 1 at the time of randomization
* French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria:

* Concurrent treatment with an investigational agent or concurrent participation in another clinical study
* Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to treatment with Octreotide for subjects randomised to receive Octreotide or the first dose of Lapatinib and Capecitabine for subjects randomised to receive no Octreotide
* Treatment with Octreotide within the 3 months prior to randomization
* Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an Epidermal growth factor receptor (EGFR) and/or HER2 inhibitor), or hormonal therapy for treatment of cancer
* Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent, unless a legally acceptable representative could provide informed consent (if in accordance with the policies of the local Ethics Committee)
* Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety or compliance with study procedures
* Diarrhoea with any grade of severity within 14 days prior to treatment with Octreotide for subjects randomised to receive Octreotide or within 14 days prior to the first dose of Lapatinib and Capecitabine for subjects randomised to receive no Octreotide
* Malabsorption syndrome, inflammatory bowel disease (ulcerative colitis, Chrohn's disease), irritable bowel syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
* Pregnant or lactating subjects
* Prior treatment with Lapatinib
* French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives, whichever is longer, preceding the first dose of protocol treatment

Primary outcomes:
measure: Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks)
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Proportion of Subjects Experiencing Diarrhoea of Grade 3 and Above (up to 24 Weeks)
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Experiencing Diarrhoea of Any Grade of Severity (up to 24 Weeks)
timeFrame: Up to 24 weeks
measure: Duration of Diarrhoea of Any Grade of Severity
timeFrame: Up to 24 weeks
measure: Time to Onset of the First Episode of Diarrhoea of Any Grade of Severity
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Taking Anti-diarrhoeal Medication
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Who Had Unscheduled Visits to Healthcare Professionals Due to Diarrhoea
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Requiring Dose Reduction in Lapatinib and Capecitabine
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Requiring Dose Delay in Lapatinib and Capecitabine
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Requiring Treatment Withdrawal in Lapatinib and Capecitabine
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Requiring Use of Diarrhoea-related Intravenous Fluids
timeFrame: Up to 24 weeks
measure: Number of Lapatinib and Capecitabine Tablets Dispensed and Returned
timeFrame: Up to 24 weeks
measure: Overall Response Rate (up to 24 Weeks)
timeFrame: Up to 24 weeks
measure: Clinical Benefit Response (up to 24 Weeks)
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Reporting Changes in Bowel Movements From Baseline (Frequency and/or Consistency) as Recorded in the Diarrhoea Management Diary (DMD)
timeFrame: Up to 24 weeks
measure: Time to the First Subject Reported Change in Frequency and/or Consistency of Bowel Movements From Baseline as Recorded in the DMD
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Taking Anti-diarrhoeal Medication as Recorded in the DMD
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Making Dietary Changes Due to Diarrhoea as Recorded in the DMD
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Contacting Other Non-hospital Healthcare Professionals to Discuss Diarrhoea as Recorded in the DMD
timeFrame: Up to 24 weeks
measure: Proportion of Subjects Reporting Stopping Completely or Missing Doses of Anti-cancer Tablets Due to Diarrhoea as Recorded in the DMD
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Konin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Khanty mansiysk
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Novartis Investigative Site
city: Obninsk
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Tomsk
country: Russian Federation
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
city: Romford
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: