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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)

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.

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

NCT ID

NCT04075955

First Posted

May 10, 2019

Last Updated

August 17, 2020

Sponsor

CR-CSSS Champlain-Charles-Le Moyne

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

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

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

Description

Time Frame

0 to 120 hours

Title

Description

Time Frame

0 to 120 hours

Title

Description

Time Frame

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

Title

Description

Quality of life score obtained according to the FLIE questionnaire

Time Frame

0 to 120 hours

Other Pre-specified Outcome Measures:

Title

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

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

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

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

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

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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