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Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy (FORESIGHT)

Primary Purpose

Chemotherapy-induced Nausea and Vomiting

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Zyprexa® (OLANZapine 5MG)
Emend® (Aprepitant)
Sponsored by
CR-CSSS Champlain-Charles-Le Moyne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chemotherapy-induced Nausea and Vomiting

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.
  • 18 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

Exclusion Criteria:

  • 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)
  • Hypersensitivity, severe reaction or allergy to one of the study treatments
  • Participation in another research protocol
  • Pregnancy or breastfeeding
  • Subject that does not have a valid phone ou email address

Sites / Locations

  • Hôpital Charles-LeMoyne

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Study treatment group

Standard treatment group

Arm Description

Olanzapine in combination with ondansetron and dexamethasone

Aprepitant in combination with ondansetron and dexamethasone

Outcomes

Primary Outcome Measures

Number of patients recruited
At least 60 patients over 5 months meet the eligibility criteria and agree to participate.
Eligible patients' interest to participate
At least 35% of all eligible patients agree to participate
Completion of the diary
At least 75% of recruited patients complete 100% of their patient diary.
Cost
The total cost of the study does not exceed 10,000$
Number of centres
The study can be done at two sites.

Secondary Outcome Measures

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.
Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete response was defined as no nausea, no vomiting and no rescue therapy. Intensity of nausea episodes will be measured with a 0 to 10 visual scale. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
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.
Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete remission was defined as no vomiting and no rescue therapy. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
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.
Proportion of patients who experienced adverse events associated with each of the treatment arms. Adverse events obtained according to the ESAS-R questionnaire and a follow-up interview at the second cycle of chemotherapy. Definition and gradation of adverse events would be following the Common Terminology Criteria for Adverse Events (CTCAE) 5th edition.
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.
Quality of life score obtained according to the FLIE questionnaire

Full Information

First Posted
May 10, 2019
Last Updated
August 17, 2020
Sponsor
CR-CSSS Champlain-Charles-Le Moyne
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1. Study Identification

Unique Protocol Identification Number
NCT04075955
Brief Title
Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy
Acronym
FORESIGHT
Official Title
FORESIGHT: Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy: a Randomised Controlled Trial Against Aprepitant in Triple Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
April 29, 2019 (Actual)
Primary Completion Date
December 31, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CR-CSSS Champlain-Charles-Le Moyne

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Nausea and Vomiting

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Study treatment group
Arm Type
Experimental
Arm Description
Olanzapine in combination with ondansetron and dexamethasone
Arm Title
Standard treatment group
Arm Type
Active Comparator
Arm Description
Aprepitant in combination with ondansetron and dexamethasone
Intervention Type
Drug
Intervention Name(s)
Zyprexa® (OLANZapine 5MG)
Other Intervention Name(s)
Zyprexa®
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Emend® (Aprepitant)
Other Intervention Name(s)
Emend®
Intervention Description
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)
Primary Outcome Measure Information:
Title
Number of patients recruited
Description
At least 60 patients over 5 months meet the eligibility criteria and agree to participate.
Time Frame
5 months
Title
Eligible patients' interest to participate
Description
At least 35% of all eligible patients agree to participate
Time Frame
5 months
Title
Completion of the diary
Description
At least 75% of recruited patients complete 100% of their patient diary.
Time Frame
5 months
Title
Cost
Description
The total cost of the study does not exceed 10,000$
Time Frame
5 months
Title
Number of centres
Description
The study can be done at two sites.
Time Frame
5 months
Secondary Outcome Measure Information:
Title
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.
Description
Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete response was defined as no nausea, no vomiting and no rescue therapy. Intensity of nausea episodes will be measured with a 0 to 10 visual scale. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
Time Frame
0 to 120 hours
Title
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.
Description
Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete remission was defined as no vomiting and no rescue therapy. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
Time Frame
0 to 120 hours
Title
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.
Description
Proportion of patients who experienced adverse events associated with each of the treatment arms. Adverse events obtained according to the ESAS-R questionnaire and a follow-up interview at the second cycle of chemotherapy. Definition and gradation of adverse events would be following the Common Terminology Criteria for Adverse Events (CTCAE) 5th edition.
Time Frame
During the complete duration of the first cycle of chemotherapy (1 cycle is 14 to 28 days)
Title
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.
Description
Quality of life score obtained according to the FLIE questionnaire
Time Frame
0 to 120 hours
Other Pre-specified Outcome Measures:
Title
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.
Description
Acute phase was defined as 0 to 24 hours following initiation of chemotherapy. Complete response was defined as no nausea, no vomiting and no rescue therapy. Intensity of nausea episodes will be measured with a 0 to 10 visual scale. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
Time Frame
0 to 24 hours
Title
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.
Description
Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete response was defined as no nausea, no vomiting and no rescue therapy. Intensity of nausea episodes will be measured with a 0 to 10 visual scale. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
Time Frame
24 to 120 hours
Title
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.
Description
Acute phase was defined as 0 to 24 hours following initiation of chemotherapy. Complete remission was defined as no vomiting and no rescue therapy. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
Time Frame
0 to 24 hours
Title
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 delayed phase.
Description
Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete remission was defined as no vomiting and no rescue therapy. Intensity of vomiting episodes will be measured with a 0 to 10 visual scale.
Time Frame
24 to 120 hours
Title
Compare rate of continuation of the same antiemetic regimen at cycle 2 between those receiving olanzapine 5mg and those receiving standard aprepitant in a triple antiemetic therapy.
Description
Proportion of patients who desire to continue the same regimen at the end of the first cycle of chemotherapy (each cycle is usually between 14 to 28 days)
Time Frame
14 to 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 18 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 Exclusion Criteria: 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) Hypersensitivity, severe reaction or allergy to one of the study treatments Participation in another research protocol Pregnancy or breastfeeding Subject that does not have a valid phone ou email address
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Prady, Md
Organizational Affiliation
CR-CISSS
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Charles-LeMoyne
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V2H1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.msss.gouv.qc.ca/inc/documents/ministere/lutte-contre-le-cancer/guides-cepo-pdf/CEPO-Anti%C3%A9m%C3%A9tiques_MAJ_(2012-11-08).pdf
Description
Prévention et traitement des nausées et vomissements induits par la chimiothérapie ou la radiothérapie chez l'adulte (Guide du CEPO)
URL
http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf
Description
NCCN Antiemesis guideline
URL
http://www.ncbi.nlm.nih.gov/pubmed/23856100
Description
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)
URL
https://pubmed.ncbi.nlm.nih.gov/30246876/
Description
Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. (Cochrane review 2018)
URL
http://www.ncbi.nlm.nih.gov/pubmed/22024310
Description
Olanzapine Versus Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Randomized Phase III Trial by Navari (2011)
URL
http://www.ncbi.nlm.nih.gov/pubmed/29330211
Description
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)
URL
http://www.ncbi.nlm.nih.gov/pubmed/28503222
Description
Olanzapine for chemotherapy-induced nausea and vomiting: systematic review and meta-analysis (Chelkeba 2017)
URL
http://www.ncbi.nlm.nih.gov/pubmed/28112422
Description
Efficacy of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting: a meta-analysis (Yang 2017)
URL
http://ncbi.nlm.nih.gov/pubmed/24770591
Description
A meta-analysis of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (Wang 2014)
URL
http://www.ncbi.nlm.nih.gov/pubmed/29039073
Description
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)
URL
https://eprovide.mapi-trust.org/instruments/functional-living-index-emesis
Description
Functional Living Index - Emesis (FLIE questionnaire)
URL
http://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-10-1
Description
A tutorial on pilot studies: the what, why and how
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761865/
Description
Clinical research of Olanzapine for prevention of chemotherapy-induced nausea and vomiting
URL
http://doi.org/10.1155/2016/3439707
Description
The Efficacy, Safety, and Cost Benefit of Olanzapine versus Aprepitant in Highly Emetogenic Chemotherapy: A Pilot Study from South India by Babu (2016)
URL
http://ncbi.nlm.nih.gov/pubmed/26768437
Description
Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis (Chiu 2016)

Learn more about this trial

Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy

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