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

NCT02861859 | Completed Phase 3 DMC

• 1 other identifier: OTT 16-05
• Study Type: interventional
• Target: 221
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Breast Cancer

Keywords

Breast cancer; Breast Carcinoma; Breast Tumors; Chemotherapy; Antiemetic effects; Antiemetic drugs; Drug Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• High personal risk overall total control of Chemotherapy-induced nausea and vomiting

  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

  3 years

• Safety of olanzapine with respect to sedation and extrapyramidal side effects in the high risk cohort

  3 years

Other Outcomes (4)

• Low personal risk of Chemotherapy-induced nausea and vomiting

  3 years

• Low personal risk overall total control of Chemotherapy-induced nausea and vomiting

  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

  3 years

Study Arms (2)

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

ACTIVE 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 (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

Interventions

Olanzapine DRUG

Olanzapine 5 mg (2 x 2.5 mg) PO OD (once a day) on days 1-4.

Also known as: Mylan-Olanzapine

Olanzapine

Olanzapine Placebo DRUG

Olanzapine Placebo 5 mg (2 x 2.5 mg) PO OD (once a day) on days 1-4.

Placebo Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital Research Institute Cance Center

Ottawa, Ontario, K1H 8L6, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Mark Clemons, MD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2016
• First Posted: August 10, 2016
• Study Start: December 1, 2016
• Primary Completion: December 23, 2019
• Study Completion: December 23, 2019
• Last Updated: February 26, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)