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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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.


Condition or disease Intervention/treatment Phase
Chemotherapy-induced Nausea and Vomiting Drug: Zyprexa® (OLANZapine 5MG) Drug: Emend® (Aprepitant) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: FORESIGHT: Feasibility of Olanzapine at REduced doSe in hIGHly Emetogenic chemoTherapy: a Randomised Controlled Trial Against Aprepitant in Triple Therapy
Actual Study Start Date : April 29, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Study treatment group
Olanzapine in combination with ondansetron and dexamethasone
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®

Active Comparator: Standard treatment group
Aprepitant in combination with ondansetron and dexamethasone
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®




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04075955


Contacts
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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

Locations
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Canada, Quebec
Hôpital Charles-LeMoyne Recruiting
Greenfield Park, Quebec, Canada, J4V2H1
Contact: Stephanie Beaulieu, BPharm, MSc    450-466-5000 ext 2280    stephanie.beaulieu.cisssmc16@ssss.gouv.qc.ca   
Contact: Annick Dufour, BPharm, MSc    450-466-5000 ext 2280    annick.dufour.cisssmc16@ssss.gouv.qc.ca   
Sponsors and Collaborators
CR-CSSS Champlain-Charles-Le Moyne
Investigators
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Principal Investigator: Catherine Prady, Md CR-CISSS
Additional Information:

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Responsible Party: CR-CSSS Champlain-Charles-Le Moyne
ClinicalTrials.gov Identifier: NCT04075955    
Other Study ID Numbers: 2019-389
First Posted: September 3, 2019    Key Record Dates
Last Update Posted: September 3, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Olanzapine
Aprepitant
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Neurokinin-1 Receptor Antagonists