Individualised Versus Standard Care for Breast Cancer Patients at High-risk for Chemotherapy-induced Nausea and Vomiting The ILIAD Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether adding olanzapine 5mg to standard antiemetic medication can significantly reduce chemotherapy-induced nausea and vomiting in breast cancer patients receiving emetogenic chemotherapy regimens such as anthracycline with cyclophosphamide-based chemotherapy and platinum-based chemotherapy. To help clinicians prescribe antiemetic medications in a more patient-centered, evidence-based and cost-effective manner, we've developed the world's first validated risk-stratification tool for chemotherapy-induced nausea and vomiting (CINV) and because of this, it is now possible to perform a trial of personalized precision antiemetic therapy for breast cancer patients. Despite widespread antiemetic use, chemotherapy-induced nausea and vomiting (CINV) remains among the most feared and expected side effects of chemotherapy for breast cancer. Inadequately controlled CINV can significantly reduce a patient's quality of life, impair functional activity, lead to chemotherapy dose delays and reductions, and even discontinuation of treatment. The merit of current antiemetic medications is based on their ability to control chemotherapy-induced vomiting, but not necessarily nausea, and nausea is the major issue for breast cancer patients. With olanzapine demonstrating significant promise in preventing acute and delayed nausea, the investigators are proposing to evaluate guideline-recommended aprepitant-based triple regimen compared to the same regimen plus olanzapine (5 mg) for patients at high personal risk for CINV. For patients at low personal risk for CINV the investigators will also evaluate guideline-recommended double antiemetic regimen compared to the same regimen plus olanzapine (5 mg).

Official Title
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A Randomized Trial of Individualised Care Versus Standard Care for Breast Cancer Patients at High Risk for Chemotherapy Induced Nausea and Vomiting. The ILIAD Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Olanzapine Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed invasive breast cancer (stage I-III) scheduled to receive neo/adjuvant anthracycline/cyclophosphamide or platinum-based chemotherapy ≥18 years Able to provide consent and complete all study-related diaries and questionnaires. Exclusion Criteria: Received previous chemotherapy Symptoms of nausea or vomiting at baseline On chronic antiemetic therapy (e.g. metoclopramide); on daily long term oral steroids prior to chemotherapy Allergic or having a medical condition that makes the administration of olanzapine, aprepitant, 5-HT3 antagonists or dexamethasone contraindicated Uncontrolled diabetes Known/documented medical/psychiatric illness that would interfere with patients' ability to complete the diary and study-related questionnaires.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Comparator<br>Eligible patients at high personal risk of CIVN will receive Standard of Care Regimen: Aprepitant (125 mg PO OD day 1, 80mg OD days 2-3), ondansetron (8mg PO, BID on Day 1 of each cycle), dexamethasone (12 mg IV x1 before chemotherapy and 4mg PO BID days 2-3) and olanzapine placebo (PO OD days 1-4). Eligible patients at low personal risk of CIVN will receive Standard of Care Regimen: Ondansetron (8mg PO, BID on Day 1 of each cycle,), dexamethasone (12 mg IV x1 before chemotherapy and 4mg PO BID days 2-3) and olanzapine placebo (PO OD days 1-4). | Drug: Olanzapine Placebo<br>* Olanzapine Placebo 5 mg (2 x 2.5 mg) PO OD (once a day) on days 1-4.<br>|
| Active Comparator: Olanzapine<br>Eligible patients at high personal risk of CIVN will receive Standard of Care Regimen: Aprepitant (125 mg PO, OD day 1, 80mg OD days 2-3), ondansetron (8mg PO, BID on Day 1 of each cycle), dexamethasone (12 mg IV x1 before chemotherapy and 4mg PO BID days 2-3) and olanzapine (5 mg PO OD days 1-4). Eligible patients at low personal risk of CIVN will receive Standard of Care Regimen: Ondansetron (8mg PO, BID on Day 1 of each cycle), dexamethasone (12 mg IV x1 before chemotherapy and 4mg PO BID days 2-3) and olanzapine (5 mg PO OD days 1-4). | Drug: Olanzapine<br>* Olanzapine 5 mg (2 x 2.5 mg) PO OD (once a day) on days 1-4.<br>* Other names: Mylan-Olanzapine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High personal risk of Chemotherapy-induced nausea and vomiting | To assess whether the addition of olanzapine to the standard antiemetic regimens significantly reduces the incidence of nausea during the overall period, over repeated cycles of chemotherapy in patients at high personal risk for Chemotherapy-induced nausea and vomiting | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High personal risk overall total control of Chemotherapy-induced nausea and vomiting | To compare overall total control of Chemotherapy-induced nausea and vomiting (i.e. no nausea, no vomiting and no use of rescue medications) between the two study arms in the high risk cohort. | 3 years | 
| Improvement of patient Health Related Quality of Life by completing a patient diary and quality of life questionnaire in the high risk cohort | To assess whether adding olanzapine to a standard antiemetic regimen significantly improves patient Health Related Quality of Life in the high risk cohort | 3 years | 
| Safety of olanzapine with respect to sedation and extrapyramidal side effects in the high risk cohort | To assess the safety of adding olanzapine as a standard antiemetic regimen particularly with respect to sedation and extrapyramidal side effects in the high risk cohort | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Breast Carcinoma, Breast Tumors, Chemotherapy, Antiemetic effects, Antiemetic drugs, Drug Therapy