Treatment of Refractory Nausea and Vomiting in Patients With Breast Cancer

NCT ID: NCT03367572

Last Updated: 2025-09-25

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1363 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-19

Study Completion Date

2024-04-13

Brief Summary

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This randomized phase III trial studies how well netupitant/palonosetron hydrochloride and dexamethasone with prochlorperazine or olanzapine work compared to netupitant/palonosetron hydrochloride and dexamethasone in improving chemotherapy-induced nausea and vomiting in patients with breast cancer. Antiemetic drugs, such as prochlorperazine and olanzapine, may help lessen nausea and vomiting in patients with breast cancer treated with chemotherapy.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine if control of nausea at cycle 2 in participants who experienced chemotherapy-induced nausea and vomiting (CINV) at cycle 1 is improved by the addition of either prochlorperazine or olanzapine to the control arm of netupitant, palonosetron and dexamethasone.

SECONDARY OBJECTIVES:

I. To determine if olanzapine is more effective than prochlorperazine in controlling nausea at cycle 2 in participants who experienced CINV at cycle 1 when used in combination with netupitant, palonosetron and dexamethasone.

II. To determine if control of vomiting at cycle 2 in patients who experienced CINV at cycle 1 is improved by the addition of either prochlorperazine or olanzapine to the control arm of netupitant, palonosetron and dexamethasone.

III. To determine if olanzapine is more effective than prochlorperazine in controlling vomiting at cycle 2 in participants who experienced CINV at cycle 1 when used in combination with netupitant, palonosetron and dexamethasone.

TERTIARY OBJECTIVES:

I. To create an empirically-based algorithm predicting nausea from breast cancer chemotherapy regimens that takes into account not only state-of-the-art anti-emetic regimens but also participant factors such as age, race, education, ethnicity, quality of life (QOL), alcohol consumption, susceptibility to nausea, expectancy, anxiety, level of nausea on the day prior to treatment, and prior history of nausea.

II. To compare the effects of the interventions on QOL, as assessed by the Functional Assessment of Cancer Therapy- General (FACT-G), by following the same procedures described under the primary aim and the first secondary aim, using change in the FACT-G scores as the response.

III. To provide preliminary data on the frequency and severity of sleep disturbance, fatigue, anxiety, and dizziness, across treatment conditions.

IV. To provide preliminary data on biological factors (e.g. glutathione \[GSH\] recycling, genetic markers) that may help identify a subgroup of patients at high risk for development of cancer-related or treatment-related side effects, or response to treatment.

OUTLINE:

PART I: Patients receive 1 cycle of standard of care chemotherapy.

PART II: Patients with a nausea score \>= 3 at least once on the diary at cycle 1 chemotherapy are randomized into 1 of 3 groups at cycle 2.

GROUP I: Within 1 hour prior to chemotherapy, patients receive netupitant/palonosetron hydrochloride orally (PO) on day 1. Within 30 minutes prior to chemotherapy, patients also receive dexamethasone PO on days 1-4. Patients also receive placebo PO with chemotherapy every 8 hours (Q8H) on days 1-4.

GROUP II: Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive prochlorperazine PO Q8H and placebo PO with chemotherapy on days 1-4.

GROUP III: Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive olanzapine PO and placebo PO Q8H with chemotherapy on days 1-4.

After completion of study treatment, patients are followed up for 30 days.

Conditions

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Breast Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Group I (netupitant/palonosetron hydrochloride, dexamethasone

Within 1 hour prior to chemotherapy, patients receive netupitant/palonosetron hydrochloride PO on day 1. Within 30 minutes prior to chemotherapy, patients also receive dexamethasone PO on days 1-4. Patients also receive placebo PO with chemotherapy Q8H on days 1-4.

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Netupitant/Palonosetron Hydrochloride

Intervention Type DRUG

Given PO

Placebo

Intervention Type OTHER

Given PO

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Group II (net/pal hydro, dexa, prochlorperazine, placebo)

Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive prochlorperazine PO Q8H and placebo PO with chemotherapy on days 1-4.

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Netupitant/Palonosetron Hydrochloride

Intervention Type DRUG

Given PO

Placebo

Intervention Type OTHER

Given PO

Prochlorperazine

Intervention Type DRUG

Given PO

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Group III (net/pal hydro, dexa, olanzapine, placebo)

Patients receive netupitant/palonosetron hydrochloride and dexamethasone as in Group I. Patients also receive olanzapine PO and placebo PO Q8H with chemotherapy on days 1-4.

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Netupitant/Palonosetron Hydrochloride

Intervention Type DRUG

Given PO

Olanzapine

Intervention Type DRUG

Given PO

Placebo

Intervention Type OTHER

Given PO

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Interventions

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Dexamethasone

Given PO

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Netupitant/Palonosetron Hydrochloride

Given PO

Intervention Type DRUG

Olanzapine

Given PO

Intervention Type DRUG

Placebo

Given PO

Intervention Type OTHER

Prochlorperazine

Given PO

Intervention Type DRUG

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone Akynzeo LY 170053 Zydis Zyprexa Zyprexa Zydis placebo therapy PLCB sham therapy RP 6140 SKF-4657 Quality of Life Assessment

Eligibility Criteria

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Inclusion Criteria

* Have a diagnosis of breast cancer and be chemotherapy naive; NOTE: prior methotrexate for non-cancerous conditions is allowed
* Be scheduled to receive a single-day chemotherapy regimen that contains doxorubicin and/or cyclophosphamide and/or carboplatin. Single-day chemotherapy is defined as only one infusion or injection per cycle. Herceptin (trastuzumab) and other chemotherapy agents will be allowed with any of these regimens
* Be scheduled to receive an antiemetic regimen that does not contain Akynzeo; in addition, the antiemetic regimen must conform with American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines at cycle 1
* Be able to read English
* Have the ability to give written informed consent
* Have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* NOTE: patients 80 years of age or older must have approval from an oncologist or their designee to participate in this study
* NOTE: patients currently receiving warfarin must have approval from an oncologist or their designee to participate in this study
* Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, or abstinence) for the duration of the study and have a negative pregnancy test within 10 days prior to the initiation of chemotherapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* CYCLE II PORTION ONLY: Only participants with a nausea score \>= 3 at least once on the diary assessment from cycle 1 can be randomized for cycle 2
* CYCLE II PORTION ONLY: Participants must be scheduled to receive the same chemotherapy regimen as received at cycle 1

Exclusion Criteria

* Have clinical evidence of current or impending bowel obstruction
* Have a known history of central nervous system disease (e.g., brain metastases or a seizure disorder)
* Have dementia
* Have uncontrolled diabetes mellitus or uncontrolled hyperglycemia
* Have severe hepatic impairment, severe renal impairment, or end-stage renal disease as determined by the treating physician
* Have had long term treatment (\> 5 days within the past 30 days) with an antipsychotic agent such as risperidone, quetiapine, clozapine, a phenothiazine, or a butyrophenone within 30 days before enrollment or plans for such treatment during the study period; NOTE: participants could have received prochlorperazine and other phenothiazines as antiemetic therapy on a short term basis (i.e., =\< 5 days)
* Have a known cardiac arrhythmia, uncontrolled congestive heart failure, or acute myocardial infarction within the previous 6 months
* Be taking benzodiazepines regularly (\> 5 days within the past 30 days); pro re nata (PRN) use (=\< 5 days) for the short-term relief of the symptoms of anxiety, anxiety associated with depressive symptoms, or as a rescue medication for breakthrough CINV is allowed
* Be taking anticholinergic medications
* Be receiving quinolone antibiotic therapy
* Be taking amifostine (Ethiofos)
* Have a known hypersensitivity to olanzapine or to phenothiazines
* CYCLE II PORTION ONLY: Must not have received Akynzeo at cycle 1
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Rochester NCORP Research Base

OTHER

Sponsor Role lead

Responsible Party

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Luke Peppone

Associate Professor of Surgery and Orthopaedics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Luke Peppone

Role: PRINCIPAL_INVESTIGATOR

University of Rochester NCORP Research Base

Locations

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Hawaii MU NCORP

Honolulu, Hawaii, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Gulf South MU-NCORP

New Orleans, Louisiana, United States

Site Status

Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

Site Status

Cancer Research Consortium of West Michigan

Grand Rapids, Michigan, United States

Site Status

Health Partners Inc

Minneapolis, Minnesota, United States

Site Status

Cancer Research for the Ozarks NCORP

Springfield, Missouri, United States

Site Status

Nevada Cancer Research Foundation NCORP

Las Vegas, Nevada, United States

Site Status

University of Rochester NCORP Research Base

Rochester, New York, United States

Site Status

Southeast Clinical Oncology Research Program

Winston-Salem, North Carolina, United States

Site Status

Columbus NCORP

Columbus, Ohio, United States

Site Status

Dayton Clinical Oncology Program

Dayton, Ohio, United States

Site Status

Geisinger Cancer Institute NCORP

Danville, Pennsylvania, United States

Site Status

Greenville NCORP

Greenville, South Carolina, United States

Site Status

Upstate Carolina NCORP

Spartanburg, South Carolina, United States

Site Status

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status

Gundersen Health System

La Crosse, Wisconsin, United States

Site Status

Aurora NCORP

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2017-00902

Identifier Type: REGISTRY

Identifier Source: secondary_id

URCC16070

Identifier Type: OTHER

Identifier Source: secondary_id

URCC-16070

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA200579

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA189961

Identifier Type: NIH

Identifier Source: secondary_id

View Link

URCC16070

Identifier Type: -

Identifier Source: org_study_id

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