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

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ClinicalTrials.gov Identifier: NCT04075955
Recruitment Status : Recruiting
First Posted : September 3, 2019
Last Update Posted : September 3, 2019
Sponsor:
Information provided by (Responsible Party):
CR-CSSS Champlain-Charles-Le Moyne

Tracking Information
First Submitted Date  ICMJE May 10, 2019
First Posted Date  ICMJE September 3, 2019
Last Update Posted Date September 3, 2019
Actual Study Start Date  ICMJE April 29, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 29, 2019)
  • Number of patients recruited [ Time Frame: 5 months ]
    At least 60 patients over 5 months meet the eligibility criteria and agree to participate.
  • Eligible patients' interest to participate [ Time Frame: 5 months ]
    At least 35% of all eligible patients agree to participate
  • Completion of the diary [ Time Frame: 5 months ]
    At least 75% of recruited patients complete 100% of their patient diary.
  • Cost [ Time Frame: 5 months ]
    The total cost of the study does not exceed 10,000$
  • Number of centres [ Time Frame: 5 months ]
    The study can be done at two sites.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2019)
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 29, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy
Official Title  ICMJE FORESIGHT: Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy: a Randomised Controlled Trial Against Aprepitant in Triple Therapy
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Chemotherapy-induced Nausea and Vomiting
Intervention  ICMJE
  • Drug: Zyprexa® (OLANZapine 5MG)

    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 Name: Zyprexa®
  • Drug: Emend® (Aprepitant)

    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 Name: Emend®
Study Arms  ICMJE
  • Experimental: Study treatment group
    Olanzapine in combination with ondansetron and dexamethasone
    Intervention: Drug: Zyprexa® (OLANZapine 5MG)
  • Active Comparator: Standard treatment group
    Aprepitant in combination with ondansetron and dexamethasone
    Intervention: Drug: Emend® (Aprepitant)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 29, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Stéphanie Beaulieu, B.Pharm, M.Sc, BCOP 450-466-5000 ext 2280 stephanie.beaulieu.cisssmc16@ssss.gouv.qc.ca
Contact: Annick Dufour, B.Pharm, M.Sc 450-466-5000 ext 3559 annick.dufour.cisssmc16@ssss.gouv.qc.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04075955
Other Study ID Numbers  ICMJE 2019-389
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party CR-CSSS Champlain-Charles-Le Moyne
Study Sponsor  ICMJE CR-CSSS Champlain-Charles-Le Moyne
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Catherine Prady, Md CR-CISSS
PRS Account CR-CSSS Champlain-Charles-Le Moyne
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP