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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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:
- •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);
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Lapatinib (Drug)
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.
干预措施: Capecitabine (Drug)
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.
干预措施: Octreotide (Drug)
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
干预措施: Lapatinib (Drug)
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
干预措施: Capecitabine (Drug)
结局指标
主要结局
Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks)
时间窗: 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)
次要结局
- Proportion of Subjects Experiencing Diarrhoea of Grade 3 and Above (up to 24 Weeks)(Up to 24 weeks)
- Proportion of Subjects Experiencing Diarrhoea of Any Grade of Severity (up to 24 Weeks)(Up to 24 weeks)
- Time to Onset of the First Episode of Diarrhoea of Any Grade of Severity(Up to 24 weeks)
- Duration of Diarrhoea of Any Grade of Severity(Up to 24 weeks)
- Proportion of Subjects Taking Anti-diarrhoeal Medication(Up to 24 weeks)
- Proportion of Subjects Requiring Treatment Withdrawal in Lapatinib and Capecitabine(Up to 24 weeks)
- Proportion of Subjects Who Had Unscheduled Visits to Healthcare Professionals Due to Diarrhoea(Up to 24 weeks)
- Proportion of Subjects Requiring Dose Reduction in Lapatinib and Capecitabine(Up to 24 weeks)
- Proportion of Subjects Requiring Dose Delay in Lapatinib and Capecitabine(Up to 24 weeks)
- Proportion of Subjects Requiring Use of Diarrhoea-related Intravenous Fluids(Up to 24 weeks)
- Number of Lapatinib and Capecitabine Tablets Dispensed and Returned(Up to 24 weeks)
- Overall Response Rate (up to 24 Weeks)(Up to 24 weeks)
- Clinical Benefit Response (up to 24 Weeks)(Up to 24 weeks)
- 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)
- 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)
- 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)
- Proportion of Subjects Taking Anti-diarrhoeal Medication as Recorded in the DMD(Up to 24 weeks)
- Proportion of Subjects Making Dietary Changes Due to Diarrhoea as Recorded in the DMD(Up to 24 weeks)
- Proportion of Subjects Contacting Other Non-hospital Healthcare Professionals to Discuss Diarrhoea as Recorded in the DMD(Up to 24 weeks)