Clinical trial NCT04075955: Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-induced Nausea and Vomiting
Lead sponsor: CR-CSSS Champlain-Charles-Le Moyne
Sponsor class: OTHER
First posted: 2019-09-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Number of patients recruited
timeFrame: 5 months
measure: Eligible patients' interest to participate
timeFrame: 5 months
measure: Completion of the diary
timeFrame: 5 months
measure: Cost
timeFrame: 5 months
measure: Number of centres
timeFrame: 5 months
Secondary outcomes:
measure: 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.
timeFrame: 0 to 120 hours
measure: 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.
timeFrame: 0 to 120 hours
measure: 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.
timeFrame: During the complete duration of the first cycle of chemotherapy (1 cycle is 14 to 28 days)
measure: 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.
timeFrame: 0 to 120 hours
Other outcomes:
measure: 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.
timeFrame: 0 to 24 hours
measure: 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.
timeFrame: 24 to 120 hours
measure: 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.
timeFrame: 0 to 24 hours
measure: 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.
timeFrame: 24 to 120 hours
measure: 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.
timeFrame: 14 to 28 days
Locations:
city: Greenfield Park
country: Canada
facility: Hôpital Charles-LeMoyne
state: Quebec
Study officials:
affiliation: CR-CISSS
name: Catherine Prady, Md
role: PRINCIPAL_INVESTIGATOR
References: