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

Phase 3
Withdrawn
Conditions
Hematopoietic and Lymphoid Cell Neoplasm
Advanced Malignant Solid Neoplasm
Interventions
Other: Questionnaire Administration
Drug: Placebo Administration
Registration Number
NCT05403580
Lead Sponsor
Mayo Clinic
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.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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 prochlorperazine 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I (olanzapine)Questionnaire AdministrationPatients receive olanzapine PO every night on days 1-28.
Arm II (placebo, olanzapine)Questionnaire AdministrationPatients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
Arm II (placebo, olanzapine)Placebo AdministrationPatients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
Arm I (olanzapine)OlanzapinePatients receive olanzapine PO every night on days 1-28.
Arm II (placebo, olanzapine)OlanzapinePatients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.
Primary Outcome Measures
NameTimeMethod
Change in nausea scoreBaseline 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.

Secondary Outcome Measures
NameTimeMethod
Daily nausea and vomiting scoresUp 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)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).

Incidence of adverse events with olanzapineUp to 28 days

Measured by patient reported outcome questionnaires and Common Terminology Criteria for Adverse Events version 5.0.

Utilization of rescue therapyUp 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).

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