Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy

NCT04075955 | Completed Phase 3

• 1 other identifier: 2019-389
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Olanzapine is frequently used off-label as an adjunct antiemetic in clinical oncology settings. North American oncology guidelines recommend it as salvage therapy and as add-on to the standard triple regimen; some suggest it may also be effective as an initial triple therapy (olanzapine replacing the NK-1 antagonist) based on phase II and III trials. This prospective, multi-center, open-label study aims to evaluate the feasibility of a large scale randomised controlled trial to compare the effectiveness and tolerability of 5mg orally once daily olanzapine in triple antiemetic therapy versus the standard treatment of aprepitant + ondansetron + dexamethasone in treatment-naive patients receiving the first cycle of a highly emetogenic chemotherapy. Secondary outcomes include effectiveness, tolerability and quality of life assessments. Effectiveness will be measured with complete response and complete remission rates in each treatment arms. Tolerability and patient quality of life will be evaluated with a standardised side effect form and validated questionnaires; ESAS-R and FLIE. The role of olanzapine-based triple therapy in prevention of chemotherapy-induced nausea and vomiting remains founded on low-quality evidence. To the investigator's knowledge, this study will be the first large scale direct comparison of 5mg olanzapine versus aprepitant in triple therapy.

Conditions

Chemotherapy-induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (5)

• Number of patients recruited

  At least 60 patients over 5 months meet the eligibility criteria and agree to participate.

  5 months

• Eligible patients' interest to participate

  At least 35% of all eligible patients agree to participate

  5 months

• Completion of the diary

  At least 75% of recruited patients complete 100% of their patient diary.

  5 months

• Cost

  The total cost of the study does not exceed 10,000$

  5 months

• Number of centres

  The study can be done at two sites.

  5 months

Secondary Outcomes (4)

• Compare effectiveness of olanzapine 5mg versus standard aprepitant in a triple antiemetic therapy in patients receiving a first cycle of highly emetogenic chemotherapy in regard of proportion of participant with complete response in the overall phase.

  0 to 120 hours

• Compare effectiveness of olanzapine 5mg versus standard aprepitant in a triple antiemetic therapy in patients receiving a first cycle of highly emetogenic chemotherapy in regard of proportion of participant with complete remission in the overall phase.

  0 to 120 hours

• Compare tolerability of olanzapine 5mg versus standard aprepitant in a triple antiemetic therapy in patients receiving a first cycle of highly emetogenic chemotherapy in regard of prevalence of adverse events due to the antiemetic therapy in each arm.

  During the complete duration of the first cycle of chemotherapy (1 cycle is 14 to 28 days)

• Compare patient's assessment of quality of life between those receiving olanzapine 5mg and those receiving standard aprepitant in a triple antiemetic therapy in patients receiving a first cycle of highly emetogenic chemotherapy.

  0 to 120 hours

Other Outcomes (5)

• Compare effectiveness of olanzapine 5mg versus standard aprepitant in a triple antiemetic therapy in patients receiving a first cycle of highly emetogenic chemotherapy in regard of proportion of participant with complete response in the acute phase.

  0 to 24 hours

• Compare effectiveness of olanzapine 5mg versus standard aprepitant in a triple antiemetic therapy in patients receiving a first cycle of highly emetogenic chemotherapy in regard of proportion of participant with complete response in the delayed phase.

  24 to 120 hours

• Compare effectiveness of olanzapine 5mg versus standard aprepitant in a triple antiemetic therapy in patients receiving a first cycle of highly emetogenic chemotherapy in regard of proportion of participant with complete remission in the acute phase.

  0 to 24 hours

Study Arms (2)

Study treatment group

EXPERIMENTAL

Olanzapine in combination with ondansetron and dexamethasone

Drug: Zyprexa® (OLANZapine 5MG)

Standard treatment group

ACTIVE COMPARATOR

Aprepitant in combination with ondansetron and dexamethasone

Drug: Emend® (Aprepitant)

Interventions

Zyprexa® (OLANZapine 5MG) DRUG

Olanzapine 5mg orally at bedtime for 4 days (starting the day before the chemotherapy) Ondansetron 16mg orally pre-chemotherapy on day 1 Dexamethasone 12mg orally pre-chemotherapy on day 1 Dexamethasone 8mg orally twice a day for 6 doses (starting on the morning of day 2)

Also known as: Zyprexa®

Study treatment group

Emend® (Aprepitant) DRUG

Aprepitant 125mg orally pre-chemotherapy on day 1, then 80mg orally once daily on days 2 and 3 Ondansetron 16mg orally pre-chemotherapy on day 1 Dexamethasone 12mg orally pre-chemotherapy on day 1 Dexamethasone 8mg orally once daily for 3 doses (starting on the morning of day 2)

Also known as: Emend®

Standard treatment group

Eligibility Criteria

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

You may qualify if:

• Patients receiving a first cycle of highly emetogenic chemotherapy (or having received one more than 2 years prior to randomisation) at the oncology outpatient clinic at Charles LeMoyne or Haut-Richelieu hospital between April 29th and September 20th 2019.
• years old and over
• Patient receiving highly emetogenic chemotherapy
• ECOG from 0 to 2 inclusively
• Creatinine clearance ≥ 30ml/min; total bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 3.0 x ULN
• Patient without electrolytic imbalance or corrected imbalance
• Signed written and informed consent

You may not qualify if:

• Patient doesn't speak french or english
• Patient to receive treatment whose protocol includes a second dose of highly emetogenic chemotherapy before day 6 of the cycle
• Patient to receive chemotherapy treatment that already contains corticosteroids (dexamethasone or prednisone) given as antineoplastic
• Nausea or vomiting present ≤ 24h before randomisation
• Untreated brain metastases
• Severe cognitive disorder or dementia or inability to properly understand or document the presence of nausea or vomiting or the use of salvage therapy
• History of uncontrolled cardiac arrhythmia, unstable angina or known QT prolongation (\> 500ms)
• Uncontrolled diabetes
• Patient to receive abdominal radiotherapy during the first cycle of chemotherapy
• Bowel obstruction, intestinal ileus or ascites present at cycle 1
• Chronic alcoholism
• Severe uncontrolled psychologic disorder
• Patient taking antipsychotic treatment on a regular basis
• Patient taking drugs with a contraindication when administered concurrently with one of the protocol drugs
• Dysphagia (incapacity to swallow the pills included in the study)

Sponsors & Collaborators

• CR-CSSS Champlain-Charles-Le Moyne: lead

Study Sites (1)

Hôpital Charles-LeMoyne

Greenfield Park, Quebec, J4V2H1, Canada

Location

Related Links

• Prévention et traitement des nausées et vomissements induits par la chimiothérapie ou la radiothérapie chez l'adulte (Guide du CEPO)
• Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting by Navari (2016)
• Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Highly or Moderately Emetogenic Chemotherapy: A Randomized, Double-Blind, Placebo-Controlled Study by Mizukami (2014)
• Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. (Cochrane review 2018)
• Olanzapine Versus Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Randomized Phase III Trial by Navari (2011)
• Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated with Highly Emetogenic Chemotherapy: A Network Meta-Analysis (Zhang 2018)
• Olanzapine for chemotherapy-induced nausea and vomiting: systematic review and meta-analysis (Chelkeba 2017)
• Efficacy of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting: a meta-analysis (Yang 2017)
• A meta-analysis of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (Wang 2014)
• A randomized pilot study comparing aprepitant to olanzapine for treatment of chemotherapy-induced nausea and vomiting by Shumway (2009)
• A double-blind randomized phase II study of 10 versus 5 mg olanzapine for emesis induced by highly emetogenic chemotherapy with cisplatin by Hashimoto (2016)
• A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy by Yanai (2018)
• Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update 2017
• Functional Living Index - Emesis (FLIE questionnaire)
• A tutorial on pilot studies: the what, why and how
• Clinical research of Olanzapine for prevention of chemotherapy-induced nausea and vomiting
• Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis (Chiu 2016)

MeSH Terms

Conditions

Vomiting

Interventions

Olanzapine; Aprepitant

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring

Study Officials

• Catherine Prady, Md

  CR-CISSS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2019
• First Posted: September 3, 2019
• Study Start: April 29, 2019
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: August 19, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)