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

• ClinicalTrials.gov Identifier: NCT05403580
• Recruitment Status: Recruiting
• First Posted: June 3, 2022
• Last Update Posted: January 6, 2023
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Tracking Information

• First Submitted Date: May 19, 2022
• First Posted Date: June 3, 2022
• Last Update Posted Date: January 6, 2023
• Actual Study Start Date: June 3, 2022
• Estimated Primary Completion Date: February 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 31, 2022)

Change in nausea score [ Time Frame: Baseline to 24 hours of treatment ]

Evaluated using Visual Analogue Scale. Nausea scores at baseline and after the first two days and the change scores, for the first 2 days, will be summarized using mean (standard deviation) and median (range). The change scores from baseline to the end of the first 2 days will be compared between arms using a two-sample t-test or a Wilcoxon rank sum test as appropriate. The difference in nausea change scores from baseline to 2 days post treatment initiation between the two arms will be estimated along with a 95% confidence interval.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 31, 2022)

• Daily nausea and vomiting scores [ Time Frame: Up to 28 days ]
  Chronic nausea this is present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale).
• Daily episodes of vomiting/retching (number and time) [ Time Frame: Up to 28 days ]
  Chronic nausea that is present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale).
• Utilization of rescue therapy [ Time Frame: Up to 28 days ]
  Baseline evaluation that includes assessment of symptom intensity for appetite, nausea, fatigue, sedation, and pain, all measured and recorded on a numeric rating score. (0 indicated the worst possible; 10, best possible).
• Incidence of adverse events with olanzapine [ Time Frame: Up to 28 days ]
  Measured by patient reported outcome questionnaires and Common Terminology Criteria for Adverse Events version 5.0.

• Original Secondary Outcome Measures: Same as current
• 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 Patients With Advanced Cancer
• Official Title: Olanzapine for the Treatment of Chronic Nausea and/or Vomiting, Unrelated to Chemotherapy or Radiation, in Advanced Cancer Patients - A Confirmatory Phase III MNCCTN Trial
• Brief Summary: This phase III trial compares olanzapine to placebo in decreasing nausea and vomiting in patients with cancer that has spread to other places in the body (advanced). Patients with advanced cancer may experience nausea and/or vomiting that is unrelated to chemotherapy or radiation. Giving olanzapine may help reduce nausea and increase appetite in patients who have advanced cancer.

Detailed Description

PRIMARY OBJECTIVE:

I. To conduct a confirmatory phase III double-blind randomized clinical trial to evaluate the ability of olanzapine to decrease nausea in patients with advanced-cancer associated nausea/vomiting.

SECONDARY OBJECTIVES:

I. To evaluate toxicity associated with olanzapine in patients with advanced-cancer associated nausea/vomiting.

II. To evaluate the effect of olanzapine on appetite, vomiting, sedation, sleep, the use of other antiemetic agents, fatigue, and well-being.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive olanzapine orally (PO) every night on days 1-28.

ARM II: Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care

Condition

• Advanced Malignant Solid Neoplasm
• Hematopoietic and Lymphoid Cell Neoplasm

Intervention

• Drug: Olanzapine
  Given PO
  Other Names:

  • LY 170053
  • Zyprexa
  • Zyprexa Zydis
• Drug: Placebo Administration
  Given PO
• Other: Questionnaire Administration
  Ancillary studies

Study Arms

• Experimental: Arm I (olanzapine)
  Patients receive olanzapine PO every night on days 1-28.
  Interventions:

  • Drug: Olanzapine
  • Other: Questionnaire Administration
• Active Comparator: Arm II (placebo, olanzapine)
  Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
  Interventions:

  • Drug: Olanzapine
  • Drug: Placebo Administration
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 31, 2022): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 15, 2024
• Estimated Primary Completion Date: February 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age >= 18 years
• Histologically or cytologically-confirmed cancer in an advanced incurable stage
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Chronic nausea that has been present for at least one week (daily score > 5, on a 0-10 visual analogue scale)
• Serum creatinine < 2.0 mg/dl =< 120 days prior to registration
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) values < 3 times upper limits of normal =< 120 days prior to registration
• Negative pregnancy test done =< 14 days prior to registration, for persons of childbearing potential only
• Able to provide written informed consent
• Able to complete questionnaire(s) by themselves or with assistance

Exclusion Criteria:

• Any of the following because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects:

  • Pregnant persons
  • Nursing persons
• Received chemotherapy or radiation within the prior 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)
• Receiving treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone for =< 30 days prior to registration or planned during protocol therapy (patients may have received prochloperazine and other phenothiazines as prior anti-emetic therapy)
• Those with concurrent use of ethyol; severe cognitive compromise; concurrent use of amifostine; concurrent use of quinolone antibiotic therapy; known hypersensitivity to olanzapine; or have planned chemotherapy or radiation during the 7 days following study initiation

• Uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection (including human immunodeficiency virus [HIV])
  • Cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
  • Psychiatric illness/social situations that would limit compliance with study requirements
• Inability to swallow oral formulations of the agent(s)
• Tube feeding or nasogastric tube

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05403580
• Other Study ID Numbers: MC211002; NCI-2022-02478 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MC211002 ( Other Identifier: Mayo Clinic in Rochester )
• Has Data Monitoring Committee: No

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: Not Provided
• Current Responsible Party: Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Charles L Loprinzi; Mayo Clinic in Rochester

• PRS Account: Mayo Clinic
• Verification Date: January 2023