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

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

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Olanzapine Placebo; Drug: Olanzapine

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Research Institute Cance Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator; 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; Olanzapine Placebo 5 mg (2 x 2.5 mg) PO OD (once a day) on days 1-4.
Active Comparator: Olanzapine; 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; Olanzapine 5 mg (2 x 2.5 mg) PO OD (once a day) on days 1-4.; Other Names: Mylan-Olanzapine

What is the study measuring?

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Mark Clemons, MD, The Ottawa Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): December 23, 2019
• Study Completion (Actual): December 23, 2019

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimate): August 10, 2016

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Drug Therapy; Breast cancer; Chemotherapy; Breast Carcinoma; Breast Tumors; Antiemetic effects; Antiemetic drugs
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Breast Diseases; Breast Neoplasms; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: OTT 16-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No