Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Gynecologic Oncology Patients

Phase III Randomized Control Trial Investigating Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Patients With Gynecologic Malignancies Receiving Every 3-week Carboplatin and Paclitaxel Chemotherapy

The objective of this study is to investigate the efficacy of olanzapine as compared to neurokinin-1 receptor antagonists (NK1-RAs) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic malignancies receiving single day outpatient chemotherapy (carboplatin and paclitaxel) every 3 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Gynecologic Cancer
• Intervention / Treatment: Drug: Ondansetron; Drug: Dexamethasone; Drug: Neurokinin-1 Receptor Antagonist (NK1-RA); Drug: Compazine; Drug: Olanzapine

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of gynecologic malignancy
• No chemotherapy in the last 12 months
• Scheduled to receive Carboplatin (AUC>=4) and Paclitaxel every three weeks
• ECOG performance status 0 or 1
• English speaking
• Willing and able to provide informed consent
• Laboratory values within protocol-defined parameters
• No vomiting in the 24 hours prior to initiating chemotherapy
• If childbearing potential exists, negative pregnancy test within 7 days prior to registration

Exclusion Criteria:

• Significant cognitive compromise
• History of CNS disease (e.g. brain metastases, seizure disorder, dementia)
• Current or recent (within 30 days) treatment with another antipsychotic agent (antidepressant medications are OK)
• Concurrent radiotherapy treatment
• Known hypersensitivity to olanzapine
• Known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the last six months
• History of diabetes mellitus on medication (insulin or oral glycemic agent)
• Alcohol abuse / chronic alcoholism
• History of closed angle glaucoma
• Current enrollment in other clinical trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nk1-RA; Nk1-RA will be given on day 1 of each 3-week chemotherapy cycle, for up to 6 cycles.	Drug: Ondansetron; 8 mg IV or 16 mg by mouth on day 1 pre-chemotherapy; then 8 mg by mouth twice a day on days 2-4 of chemotherapy; Drug: Dexamethasone; 20 mg IV on day 1 pre-chemotherapy; Drug: Neurokinin-1 Receptor Antagonist (NK1-RA); 150 mg IV on day 1 pre-chemotherapy; Other Names: Fosaprepitant; Drug: Compazine; 5-10 mg by mouth, available as needed, every 6 hours, days 1-5
Experimental: Olanzapine; Olanzapine will be given on days 1-4 of each 3-week chemotherapy cycle, for up to 6 cycles.	Drug: Ondansetron; 8 mg IV or 16 mg by mouth on day 1 pre-chemotherapy; then 8 mg by mouth twice a day on days 2-4 of chemotherapy; Drug: Dexamethasone; 20 mg IV on day 1 pre-chemotherapy; Drug: Compazine; 5-10 mg by mouth, available as needed, every 6 hours, days 1-5; Drug: Olanzapine; 5 mg by mouth on days 1-4 of chemotherapy (taken at night); Other Names: Zyprexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complete response in the overall time period (0 - 120 hours post-chemotherapy)	Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome.	At day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complete response in the acute time period (0 - 24 hours post-chemotherapy)	Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome.	At day 2
Rate of complete response in the delayed time period (24 - 120 hours post-chemotherapy)	Complete response (CR) is defined as no episodes of vomiting and no use of rescue antiemetic medications. Patient reported diaries will be used to measure this outcome.	At day 6
Rate of no nausea in the acute time period (0 - 24 hours post-chemotherapy)	Patients will record daily levels of nausea after chemotherapy using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea).	At day 2
Rate of no nausea in the delayed time period (24 - 120 hours post-chemotherapy)	Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea).	At day 6
Rate of no nausea in the overall time period (0 - 120 hours post-chemotherapy)	Patients will record daily levels of nausea using a Likert scale ranging from 0-10 (0 indicating no nausea; 10 indicating maximum level of nausea).	At day 6
Mean somnolence score	Patients will record daily levels of undesired sedation using a Likert scale ranging from 0 to 10 (0 indicating no undesired sedation; 10 indicating maximum level of undesired sedation).	At day 6
Mean increased-appetite score	Patients will record daily levels of undesired increase in appetite using a Likert scale ranging from 0 to 10 (0 indicating no undesired increase in appetite; 10 indicating maximum level of undesired increase in appetite).	At day 6

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Aimee Rolston, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2020
• Primary Completion (Actual): January 3, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Selective Serotonin Reuptake Inhibitors; Dexamethasone; Olanzapine; Ondansetron; Fosaprepitant; Prochlorperazine; Neurokinin-1 Receptor Antagonists
• Other Study ID Numbers: UMCC 2019.173; HUM00175458 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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