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NCT Number: NCT04075955

Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy

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.

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Key information

Conditions

Chemotherapy-induced Nausea and Vomiting Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive Vomiting

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hôpital Charles-LeMoyne

Greenfield Park, Quebec, J4V2H1, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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)

Other names: Zyprexa®

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)

Other names: Emend®

Primary outcomes

  1. Number of patients recruited

    Time frame: 5 months

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

  2. Eligible patients' interest to participate

    Time frame: 5 months

    At least 35% of all eligible patients agree to participate

  3. Completion of the diary

    Time frame: 5 months

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

  4. Cost

    Time frame: 5 months

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

  5. Number of centres

    Time frame: 5 months

    The study can be done at two sites.

Secondary outcomes

  1. 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.

    Time frame: 0 to 120 hours

    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.

  2. 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.

    Time frame: 0 to 120 hours

    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.

  3. 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.

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

    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.

  4. 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.

    Time frame: 0 to 120 hours

    Quality of life score obtained according to the FLIE questionnaire

Other outcomes

  1. 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.

    Time frame: 0 to 24 hours

    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.

  2. 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.

    Time frame: 24 to 120 hours

    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.

  3. 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.

    Time frame: 0 to 24 hours

    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.

  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 remission in the delayed phase.

    Time frame: 24 to 120 hours

    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.

  5. 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.

    Time frame: 14 to 28 days

    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)

Sponsors and collaborators

Lead sponsor

CR-CSSS Champlain-Charles-Le Moyne

Other

Registry information

Official study title

FORESIGHT: Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy: a Randomised Controlled Trial Against Aprepitant in Triple Therapy

Acronym: FORESIGHT

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
Sep 3, 2019
Registry last updated
Aug 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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