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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Advanced Malignant Solid Neoplasm
• Intervention / Treatment: Other: Questionnaire Administration; Drug: Placebo Administration; Drug: Olanzapine

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
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Grand Rapids, Minnesota, United States, 55744
      • Recruiting
      • Fairview Grand Itasca Clinic and Hospital
      • Contact: Anastas Provatas, M.D.; Phone Number: 612-624-2620; Email: ccinfo@umn.edu
      • Principal Investigator: Anastas Provatas, M.D.
    • Hibbing, Minnesota, United States, 55746
      • Recruiting
      • Fairview Range Medical Center
      • Contact: Anastas Provatas, M.D.; Phone Number: 612-624-2620; Email: ccinfo@umn.edu
      • Principal Investigator: Anastas Provatas, M.D.
    • Mankato, Minnesota, United States, 56001
      • Recruiting
      • Mayo Clinic Health System Mankato
      • Principal Investigator: Stephan D. Thome
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
    • Monticello, Minnesota, United States, 55362
      • Recruiting
      • MMCORC CentraCare Monticello Cancer Center
      • Contact: Yan Ji, M.D.; Phone Number: 612-624-2620; Email: ccinfo@umn.edu
      • Principal Investigator: Yan Ji, M.D.
    • Princeton, Minnesota, United States, 55371
      • Recruiting
      • Fairview Northland Medical Center
      • Contact: Anastas Provatas, M.D.; Phone Number: 612-624-2620; Email: ccinfo@umn.edu
      • Principal Investigator: Anastas Provatas, M.D.
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Clinical Trial Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Charles L. Loprinzi, M.D.
    • Worthington, Minnesota, United States, 56187
      • Recruiting
      • Sanford Health Worthington
      • Contact: Jonathan Bleeker, M.D.; Phone Number: 612-624-2620; Email: ccinfo@umn.edu
      • Principal Investigator: Jonathan Bleeker, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (olanzapine); Patients receive olanzapine PO every night on days 1-28.	Other: Questionnaire Administration; Ancillary studies; Drug: Olanzapine; Given PO; Other Names: Zyprexa; Zyprexa Zydis; LY 170053
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.	Other: Questionnaire Administration; Ancillary studies; Drug: Placebo Administration; Given PO; Drug: Olanzapine; Given PO; Other Names: Zyprexa; Zyprexa Zydis; LY 170053

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in nausea score	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.	Baseline to 24 hours of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily nausea and vomiting scores	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).	Up to 28 days
Daily episodes of vomiting/retching (number and time)	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).	Up to 28 days
Utilization of rescue therapy	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).	Up to 28 days
Incidence of adverse events with olanzapine	Measured by patient reported outcome questionnaires and Common Terminology Criteria for Adverse Events version 5.0.	Up to 28 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles L Loprinzi, Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2022
• Primary Completion (Actual): December 29, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Neoplasms; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Olanzapine
• Other Study ID Numbers: MC211002 (Other Identifier: Mayo Clinic in Rochester); NCI-2022-02478 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 21-011317 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No