Olanzapine for the Treatment of Chronic Nausea and/or Vomiting in Advanced Cancer Patients

• ClinicalTrials.gov Identifier: NCT03137121
• Recruitment Status: Completed
• First Posted: May 2, 2017
• Results First Posted: August 17, 2021
• Last Update Posted: August 17, 2021
• Sponsor: University of Alabama at Birmingham
• Collaborator: Mayo Clinic
• Information provided by (Responsible Party): Rudolph Navari, University of Alabama at Birmingham

Tracking Information

• First Submitted Date: April 25, 2017
• First Posted Date: May 2, 2017
• Results First Submitted Date: August 13, 2020
• Results First Posted Date: August 17, 2021
• Last Update Posted Date: August 17, 2021
• Actual Study Start Date: July 12, 2017
• Actual Primary Completion Date: July 12, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2021)

Mean Nausea Scores [ Time Frame: Nausea score from the Visual Analogue Scale will be recorded each day daily for 7 days. An average value calculated will be reported for the 7 day period. ]

Daily nausea scores (the primary objective) on day 1 to 7 of treatment for each patient from the Olanzapine and Placebo group will be measured using the Visual Analogue Scale rankings from 0-10 where 0 is no nausea and 10 is the maximum nausea experienced by a patient. A Visual Analogue Scale is a psychometric response scale which can be used in questionnaires. It is a measurement instrument for subjective characteristics or attitudes that can't be directly measured. Patients will be asked to record the average nausea score for each day in a diary and a study nurse will call the patient at the same time each day to remind the patient to record the nausea score and to inquire about any toxicities. The difference in the nausea scores for the patients in each group (Olanzapine and Placebo) will be compared.

Original Primary Outcome Measures (submitted: April 27, 2017)

Effect of olanzapine [ Time Frame: Nausea score from the Visula Analogue Scale will be recorded each day daily for 7 days ]

Daily nausea scores (the primary objective) on day 1 to 7 of treatment for each patient from Groups 1 and 2 will be measured using the Visual Analogue Scale rankings from 0-10 where 0 is no nausea and 10 is the maximum nausea experienced by a patient. Patients will be asked to record the average nause score for each day in a diary and a study nurse will call the patient at the same time each day to remind the patient to record the nausea score and to inquire about any toxicities. The difference in the nausea scores for the patients in each group (Group 1 and Group 2) will be compared.

Current Secondary Outcome Measures (submitted: July 23, 2021)

• Number of Emetic Episodes [ Time Frame: Number of emetic episodes for each patient on each day of the seven day treatment. ]
  The number of emetic episodes (a secondary outcome) by each patient in each group, Olanzapine & Placebo, on each day of treatment will be recorded by each patient on each day of treatment in a diary. A study nurse will contact each patient at the same time of each day of the study to ask the patient to record the number of emetic episodes and report any toxicities.The number of emetic episodes for the patients in each Group for each day of the treatment will be compared.
• Number of Treatment-related Adverse Events as Assessed by CTCAE v4.0". [ Time Frame: Daily assessment for 7 days for each patient in Olanzapine & Placebo Groups. ]
  Adverse events will be measured by patient-reported outcomes questionnaires and the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A study nurse will contact each patient each day of the seven days of treatment to inquire about any toxicities, specifically sedation and appetite. Sedation and appetite will be reported by the patient in each Group on a Visual Analogue Scale of 0 to 10 with 0 being no sedation or no appetite to 10 indicating maximum sedation or maximum appetite.

Original Secondary Outcome Measures (submitted: April 27, 2017)

• Effect of Olanzapine [ Time Frame: Number of emetic episodes for each patient on each day of the seven day treatment. ]
  The number of emetic episodes (a secondary outcome) by each patient in each Group (1 and 2) on each day of treatment will be recorded by each patient on each day of treatment in a diary. A study nurse will contact each patient at the same time of each day of the study to ask the patient to record the number of emetic episodes and report any toxicities.The number of emetic episodes for the patients in each Group for each day of the treatment will be compared.
• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0". [ Time Frame: Daily assessment for 7 days for each patient in Groups 1 and 2 ]
  Adverse events will be measured by patient-reported outcomes questionnaires and the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A study nurse will contact each patient each day of the seven days of treatment to inquire about any toxicities, specifically sedation and appetite. Sedation and appetite will be reported by the patient in each Group on a Visual Analoge Scale of 0 to 10 with 0 being no sedation or no appetitie to 10 indicating maximum sdation or maximum appetite.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Olanzapine for the Treatment of Chronic Nausea and/or Vomiting in Advanced Cancer Patients
• Official Title: Olanzapine for the Treatment of Chronic Nausea and/or Vomiting, Unrelated to Chemotherapy or Radiation, in Advanced Cancer Patient - A Pilot, Dose-Finding Trial
• Brief Summary: The purpose of this study is to evaluate the use of olanzapine for the treatment of cancer patients with chronic nausea and/or vomiting unrelated to chemotherapy or radiation in a randomized placebo-controlled pilot trial.
• Detailed Description: Patients with advanced cancer experience a variety of physical and psychosocial symptoms that significantly affect the patients' quality of life. Chronic nausea is a particularly distressing symptom present in >60% of patients with advanced cancer. A number of palliative care studies have evaluated treatments of nausea with limited success. Olanzapine with its unique formulation and decreased drug interactions compared to many other drugs appears to be a reasonable candidate for further evaluation. Olanzapine has significant potential for use in the prevention and treatment of nausea in a palliative care setting with a once-daily dosing.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

There will be two groups for the study: Olanzapine Group will receive the study drug and Placebo Group will receive a placebo.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Patients will receive the study drug or placebo in a double-blind fashion.

Primary Purpose: Treatment

• Condition: Advanced Cancer

Intervention

• Drug: Olanzapine
  Olanzapine is used as an anti-emetic.
  Other Name: Zyprexa
• Other: Placebo
  The placebo is a non-anti-emetic.

Study Arms

• Experimental: Olanzapine
  Patients will receive 5 mg olanzapine orally for 1 to 7 days daily.
  Intervention: Drug: Olanzapine
• Placebo Comparator: Placebo
  Patients will receive a placebo orally for 1 to 7 days daily.
  Intervention: Other: Placebo

• Publications *: Navari RM, Pywell CM, Le-Rademacher JG, White P, Dodge AB, Albany C, Loprinzi CL. Olanzapine for the Treatment of Advanced Cancer-Related Chronic Nausea and/or Vomiting: A Randomized Pilot Trial. JAMA Oncol. 2020 Jun 1;6(6):895-899. doi: 10.1001/jamaoncol.2020.1052.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 27, 2017): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 15, 2020
• Actual Primary Completion Date: July 12, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Be at least 18 years of age
• Have histologically or cytologically-confirmed malignant disease in an advanced incurable stage
• Have not received chemotherapy or radiation for >14 days (advanced cancer patients receiving hormonal therapy or targeted therapy that does not come with a recommendation for prophylactic anti-emetic therapy are eligible)
• Have chronic nausea that has been present for at least one week (worst daily score >3, 0-10 visual analogue scale) or vomiting at least five times over past one week
• Have serum creatinine < 2.0 mg/dl and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) < 3 times upper limits of normal ≤120 days prior to registration
• Absolute neutrophil count (ANC) >1500 mm3 <120 days prior to registration
• Women of childbearing potential must consent to use adequate contraception throughout protocol therapy; females of childbearing potential must have a negative urine pregnancy test <7 days prior to registration.

Exclusion Criteria:

• Not be receiving treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone for less than or equal to 30 days prior to registration or planned during protocol therapy (patients may have received prochlorperazine and other phenothiazines as prior anti-emetic therapy)
• Not have concurrent use of ethyol
• Not have severe cognitive compromise
• History of central nervous system (CNS) disease (e.g. brain metastases, seizure disorder)
• Concurrent use of amifostine, concurrent abdominal radiotherapy; concurrent use of quinolone antibiotic therapy
• Chronic alcoholism (as determined by the investigator)
• Known hypersensitivity to olanzapine
• Known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the previous six months
• History of uncontrolled diabetes mellitus (stable insulin dose and/or stable oral hypoglycemic agent permitted)
• Planned chemotherapy or radiation during the 7 days following study initiation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03137121
• Other Study ID Numbers: F170104006 (XUAB 16100); 000515449 ( Other Identifier: UAB Office of Sponsored Programs )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Rudolph Navari, University of Alabama at Birmingham
• Study Sponsor: University of Alabama at Birmingham
• Collaborators: Mayo Clinic

Investigators

• Principal Investigator: Rudolph Navari, MD; University of Alabama at Birmingham

• PRS Account: University of Alabama at Birmingham
• Verification Date: July 2021