Birmingham, Alabama 35233

  • Malignant Neoplasm

Purpose:

This randomized phase III trial studies how well olanzapine with or without fosaprepitant work in preventing chemotherapy induced nausea and vomiting in cancer patients receiving chemotherapy that causes vomiting. Olanzapine and fosaprepitant dimeglumine may help control nausea and vomiting in patients during chemotherapy. Olanzapine is usually given in combination with other drugs, including fosaprepitant dimeglumine. It is not yet known if olanzapine when given with other drugs, is still effective without using fosaprepitant dimeglumine for controlling nausea and vomiting.


Study summary:

PRIMARY OBJECTIVES: I. To compare between the two study arms the proportion of patients with no nausea for the overall (0-120 hours post-chemotherapy), acute (0-24 hours post-chemotherapy), and delayed periods (24-120 hours post-chemotherapy) for patients receiving highly emetogenic chemotherapy (HEC). SECONDARY OBJECTIVES: I. To compare between the two study arms the complete response (CR) rates (no emetic episodes and no use of rescue medication) in the acute, delayed, and overall periods. II. To compare between the two study arms, the incidences of potential toxicities that have been ascribed to olanzapine. III. To perform an economic evaluation of olanzapine and fosaprepitant dimeglumine (fosaprepitant) versus (vs.) olanzapine in patients receiving HEC (noting that all patients will also receive dexamethasone and a 5HT3 receptor antagonist). IV. To explore the efficacy of olanzapine in chemotherapy cycles two to four, for patients who elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy cycles two to four (continuation phase), by documenting nausea and complete response. V. To explore the safety of olanzapine in chemotherapy cycles two to four, for patients who elect to continue on the same antiemetic regimen received in cycle one, in chemotherapy cycles two to four (continuation phase), by recording any adverse events or drug related toxicities. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive palonosetron hydrochloride intravenously (IV) over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or orally (PO) on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed up periodically.


Criteria:

Inclusion Criteria: - Diagnosis of malignant disease of any stage; (stage I through stage IV) - No prior history of chemotherapy for any malignancy - Scheduled to receive intravenous HEC (highly emetogenic chemotherapy) (either cisplatin-containing regimen or doxorubicin and cyclophosphamide [AC]); cisplatin, given on a single day, at a dose of >= 70 mg/m^2, with or without other chemotherapy agent(s) OR doxorubicin (60 mg/m^2) plus cyclophosphamide (600 mg/m^2) - No nausea or vomiting =< 24 hours prior to registration - Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for women of childbearing potential only * A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) - No known diagnosis of dementia; patients with stable treated brain metastases are eligible to participate - No known history of central nervous system (CNS) disease (e.g. seizure disorder) - No treatment with another antipsychotic agent such as olanzapine, risperidone, quetiapine, clozapine, phenothiazine or butyrophenone =< 30 days prior to registration - No chronic phenothiazine administration as an antipsychotic agent (patients may receive prochlorperazine and other phenothiazines as rescue anti-emetic therapy but not within 24 hours prior to registration) - No use of amifostine within 7 days prior to registration - No radiotherapy within 7 days prior to registration or planned for one week after the current dose of chemotherapy - No use of quinolone antibiotic therapy within 7 days prior to registration - No chronic alcoholism (as determined by the investigator) - No known hypersensitivity to olanzapine - No known uncontrolled cardiac arrhythmia, no known uncontrolled congestive heart failure, or no acute myocardial infarction within the previous six months - No history of uncontrolled diabetes mellitus, i.e., no diabetic ketoacidosis; within 6 months prior to registration; patients are eligible if they have controlled diabetes on diet, oral agents, and/or insulin - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 - Patients must be able to read and comprehend English; local translation, including verbal translation of patient-reported outcomes (PROs) is not permitted - Serum creatinine =< 2.0 mg/dL =< 120 days prior to registration - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) =< 120 days prior to registration


Study is Available At:


Original ID:

A221602


NCT ID:

NCT03578081


Secondary ID:

NCI-2017-02410


Study Acronym:


Brief Title:

Olanzapine With or Without Fosaprepitant Dimeglumine in Preventing Chemotherapy Induced Nausea and Vomiting in Cancer Patients Receiving Highly Emetog


Official Title:

Olanzapine With or Without Fosaprepitant for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV)in Patients Receiving Highly Emetogenic Chemotherapy (HEC): A Phase III Randomized, Double Blind, Placebo-Controlled Trial


Overall Status:

Active, not recruiting


Study Phase:

Phase 3


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Alliance for Clinical Trials in Oncology


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

690


Enrollment Type:

Actual


Overall Contact Information

Official Name:Rudolph Navari, MD, PhD, FACP
Study Chair
University of Alabama at Birmingham

Study Dates

Start Date:October 15, 2018
Completion Date:August 2023
Completion Type:Anticipated
Primary Completion Date:November 8, 2021
Primary Completion Type:Actual
Verification Date:January 2022
Last Changed Date:January 6, 2022
First Received Date:June 25, 2018

Study Outcomes

Outcome Type:Primary Outcome
Measure:No nausea rate defined as a response of 0 in the nausea item of Nausea and Vomiting Daily Diary/Questionnaire in the overall (0-120 hours), acute (0-24 hours), and delayed (24-120 hours) periods
Time Frame:Up to 120 hours
Safety Issues:False
Description:The specific measure will be based on the proportion of patients with a value of 0, as measured by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Questionnaire. A modified intent-to-treat principle will be applied for s
Outcome Type:Secondary Outcome
Measure:Complete response (CR) (no emetic episodes and no use of rescue medication) during the acute, delayed and the overall periods as measured by the Nausea and Vomiting Daily Diary/Questionnaire
Time Frame:Up to 120 hours
Safety Issues:False
Description:The specific measure will be based on the proportion of patients who answered "None" to both questions concerning Vomiting episode(None, Once, Twice, More than twice) and number of extra nausea/vomiting pills taken (None, One, Two, More than two) in the N
Outcome Type:Secondary Outcome
Measure:Potential toxicities as ascribed to olanzapine as measured by the Nausea and Vomiting Daily Diary/Questionnaire
Time Frame:Up to 1 year
Safety Issues:False
Description:Potential toxicities includes nausea, undesired sedation, and undesired appetite, measured by three individual items ( nausea, undesired sedation, undesired appetite) of the Nausea and Vomiting Daily Dairy/Questionnaire(scale 0-10, 0 is no symptoms, 10 is
Outcome Type:Secondary Outcome
Measure:Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/Questionnaire
Time Frame:Up to 1 year
Safety Issues:False
Description:The specific measure will be based on the by the single nausea item (scale 0-10, 0 is no symptoms, 10 is worst symptoms) of the Nausea and Vomiting Daily Diary/Questionnaire. Nausea scores (0-10) repeatedly measured by the Nausea and Vomiting Daily Diary/
Outcome Type:Secondary Outcome
Measure:Frequency of rescue medication as measured by the Nausea and Vomiting Daily Diary/Questionnaire
Time Frame:Up to 1 year
Safety Issues:False
Description:The specific measure will be based on the single item : number of extra nausea/vomiting pills taken (None, One , Twice, More than twice) of the Nausea and Vomiting Daily Diary/Questionnaire. The proportion of patients taking any rescue medication as repor

Study Interventions

Intervention Type:Drug
Name:Palonosetron Hydrochloride
Description:Given IV
Arm Name:Arm I (fosaprepitant dimeglumine, olanzapine)
Intervention Type:Drug
Name:Ondansetron Hydrochloride
Description:Given IV or PO
Arm Name:Arm I (fosaprepitant dimeglumine, olanzapine)
Intervention Type:Drug
Name:Dexamethasone
Description:Given PO
Arm Name:Arm I (fosaprepitant dimeglumine, olanzapine)
Intervention Type:Drug
Name:Fosaprepitant Dimeglumine
Description:Given IV
Arm Name:Arm I (fosaprepitant dimeglumine, olanzapine)
Intervention Type:Drug
Name:Olanzapine
Description:Given PO
Arm Name:Arm I (fosaprepitant dimeglumine, olanzapine)
Intervention Type:Other
Name:Placebo
Description:Given IV
Arm Name:Arm II (placebo, olanzapine)

Study Arms

Study Arm Type:Active Comparator
Arm Name:Arm II (placebo, olanzapine)
Description:Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, placebo IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment (with no placebo) may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Study Arm Type:Experimental
Arm Name:Arm I (fosaprepitant dimeglumine, olanzapine)
Description:Patients receive palonosetron hydrochloride IV over 30 seconds or ondansetron hydrochloride IV over 2-5 minutes or PO on day 1, dexamethasone PO on days 1-4, fosaprepitant dimeglumine IV over 20-30 minutes on day 1, and olanzapine PO on days 1-4. Treatment may repeat every 4 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Alliance for Clinical Trials in Oncology
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: February 07, 2023

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