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

Sponsor

University of Michigan Rogel Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04503668

Collaborator

(none)

170

Enrollment

Location

Arms

23.1

Anticipated Duration (Months)

7.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gynecologic Cancer	Drug: Ondansetron Drug: Dexamethasone Drug: Neurokinin-1 Receptor Antagonist (NK1-RA) Drug: Olanzapine Drug: Compazine	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

170 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Dec 28, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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: Olanzapine 5 mg by mouth on days 1-4 of chemotherapy (taken at night) Other Names: Zyprexa Drug: Compazine 5-10 mg by mouth, available as needed, every 6 hours, days 1-5

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: Olanzapine

5 mg by mouth on days 1-4 of chemotherapy (taken at night)

Other Names:

Zyprexa

Drug: Compazine

5-10 mg by mouth, available as needed, every 6 hours, days 1-5

Outcome Measures

Primary Outcome Measures

Rate of complete response in the overall time period (0 - 120 hours post-chemotherapy) [At day 6]
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.

Secondary Outcome Measures

Rate of complete response in the acute time period (0 - 24 hours post-chemotherapy) [At day 2]
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.
Rate of complete response in the delayed time period (24 - 120 hours post-chemotherapy) [At day 6]
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.
Rate of no nausea in the acute time period (0 - 24 hours post-chemotherapy) [At day 2]
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).
Rate of no nausea in the delayed time period (24 - 120 hours post-chemotherapy) [At day 6]
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).
Rate of no nausea in the overall time period (0 - 120 hours post-chemotherapy) [At day 6]
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).
Mean somnolence score [At day 6]
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).
Mean increased-appetite score [At day 6]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 89 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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