Netupitant/Palonosetron Hydrochloride and Dexamethasone With or Without Prochlorperazine or Olanzapine in Improving Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer

April 10, 2024 updated by: Luke Peppone, University of Rochester NCORP Research Base

Treatment of Refractory Nausea

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

1600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
    • Illinois
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Decatur Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Recruiting
        • Gulf South MU-NCORP
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Cancer Research Consortium of West Michigan
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
    • Missouri
      • Springfield, Missouri, United States, 65804
        • Recruiting
        • Cancer Research for the Ozarks NCORP
        • Contact:
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Recruiting
        • Nevada Cancer Research Foundation NCORP
        • Contact:
    • New York
      • Rochester, New York, United States, 14642
        • Active, not recruiting
        • University of Rochester NCORP Research Base
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27104
        • Recruiting
        • Southeast Clinical Oncology Research Program
        • Contact:
    • Ohio
      • Columbus, Ohio, United States, 43215
      • Dayton, Ohio, United States, 45459
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Recruiting
        • Geisinger Cancer Institute NCORP
        • Contact:
    • South Carolina
      • Greenville, South Carolina, United States, 29615
        • Recruiting
        • Greenville NCORP
        • Contact:
      • Spartanburg, South Carolina, United States, 29303
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Recruiting
        • Saint Vincent Hospital Cancer Center Green Bay
        • Principal Investigator:
          • Brian L. Burnette
        • Contact:
      • La Crosse, Wisconsin, United States, 54601
      • Milwaukee, Wisconsin, United States, 53226

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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
  • CYCLE II PORTION ONLY: Must still meet all the exclusion criteria for cycle 1

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Drug: Dexamethasone
Given PO
Other Names:
  • Decadron
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • 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
Drug: Netupitant/Palonosetron Hydrochloride
Given PO
Other Names:
  • Akynzeo
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Drug: Dexamethasone
Given PO
Other Names:
  • Decadron
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • 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
Drug: Netupitant/Palonosetron Hydrochloride
Given PO
Other Names:
  • Akynzeo
Drug: Prochlorperazine
Given PO
Other Names:
  • RP 6140
  • SKF-4657
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Drug: Dexamethasone
Given PO
Other Names:
  • Decadron
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • 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
Drug: Netupitant/Palonosetron Hydrochloride
Given PO
Other Names:
  • Akynzeo
Drug: Olanzapine
Given PO
Other Names:
  • Zyprexa
  • Zyprexa Zydis
  • Zydis
  • LY 170053

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average nausea defined as the average nausea rating across 15 assessment points (comparing prochlorperazine or olanzapine to control arm)
Time Frame: Up to day 4
Will be measured on a 7-point scale anchored by "not at all nauseated" and "extremely nauseated".
Up to day 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average nausea defined as the average nausea rating across 15 assessment points (comparing olanzapine to prochlorperazine)
Time Frame: Up to day 4
Will be measured on a 7-point scale anchored by "not at all nauseated" and "extremely nauseated".
Up to day 4
Presence of any vomiting (yes or no)
Time Frame: Up to day 4
Will assess presence of any vomiting (yes or no).
Up to day 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rochester NCORP Research Base

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Luke Peppone, University of Rochester NCORP Research Base

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 19, 2018

Primary Completion (Estimated)

April 1, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

December 4, 2017

First Submitted That Met QC Criteria

December 7, 2017

First Posted (Actual)

December 8, 2017

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • URCC16070 (Other Identifier: University of Rochester NCORP Research Base)
  • UG1CA189961 (U.S. NIH Grant/Contract)
  • NCI-2017-00902 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • URCC-16070 (Other Identifier: DCP)
  • R01CA200579 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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