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

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ClinicalTrials.gov Identifier: NCT03367572
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : October 23, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Luke Peppone, University of Rochester NCORP Research Base

Tracking Information
First Submitted Date  ICMJE December 4, 2017
First Posted Date  ICMJE December 8, 2017
Last Update Posted Date October 23, 2020
Actual Study Start Date  ICMJE March 9, 2018
Estimated Primary Completion Date December 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2017)
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".
Original Primary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
Average nausea defined as the average nausea rating across 15 assessment points [ Time Frame: Up to day 4 ]
Will be measured on a 7-point scale anchored by "not at all nauseated" and "extremely nauseated".
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2017)
  • 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".
  • Presence of any vomiting (yes or no) [ Time Frame: Up to day 4 ]
    Will assess presence of any vomiting (yes or no).
Original Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • Average nausea defined as the average nausea rating across 15 assessment points [ Time Frame: Up to day 4 ]
    Will be measured on a 7-point scale anchored by "not at all nauseated" and "extremely nauseated".
  • Presence of any vomiting (yes or no) [ Time Frame: Up to day 4 ]
    Will assess presence of any vomiting (yes or no).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Netupitant/Palonosetron Hydrochloride and Dexamethasone With or Without Prochlorperazine or Olanzapine in Improving Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer
Official Title  ICMJE Treatment of Refractory Nausea
Brief Summary 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

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Condition  ICMJE Breast Carcinoma
Intervention  ICMJE
  • Drug: Dexamethasone
    Given PO
    Other Names:
    • 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
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Netupitant/Palonosetron Hydrochloride
    Given PO
    Other Name: Akynzeo
  • Drug: Olanzapine
    Given PO
    Other Names:
    • LY 170053
    • Zydis
    • Zyprexa
    • Zyprexa Zydis
  • Other: Placebo
    Given PO
    Other Names:
    • placebo therapy
    • PLCB
    • sham therapy
  • Drug: Prochlorperazine
    Given PO
    Other Names:
    • RP 6140
    • SKF-4657
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Netupitant/Palonosetron Hydrochloride
    • Other: Placebo
    • Other: Quality-of-Life Assessment
  • 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.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Netupitant/Palonosetron Hydrochloride
    • Other: Placebo
    • Drug: Prochlorperazine
    • Other: Quality-of-Life Assessment
  • 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.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Netupitant/Palonosetron Hydrochloride
    • Drug: Olanzapine
    • Other: Placebo
    • Other: Quality-of-Life Assessment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 21, 2020)
1200
Original Estimated Enrollment  ICMJE
 (submitted: December 7, 2017)
800
Estimated Study Completion Date  ICMJE May 1, 2023
Estimated Primary Completion Date December 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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; 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03367572
Other Study ID Numbers  ICMJE URCC16070
NCI-2017-00902 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
URCC16070 ( Other Identifier: University of Rochester NCORP Research Base )
URCC-16070 ( Other Identifier: DCP )
R01CA200579 ( U.S. NIH Grant/Contract )
UG1CA189961 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Luke Peppone, University of Rochester NCORP Research Base
Study Sponsor  ICMJE University of Rochester NCORP Research Base
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Luke Peppone University of Rochester NCORP Research Base
PRS Account University of Rochester
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP