Treatment of Refractory Nausea and Vomiting in Patients With Breast Cancer

NCT03367572 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: URCC16070NCI-2017-00902URCC-16070R01CA200579UG1CA189961
• Study Type: interventional
• Target: 1,363
• Locations: 1 country
• Sites: 18

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.

Conditions

Breast Carcinoma

Outcome Measures

Primary Outcomes (2)

• Average Nausea Defined as the Average [ MAXIMUM ] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm)

  Will be measured on a 7-point scale ("1: not at all nauseated", "4: moderately nauseated", "7: extremely nauseated"). Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 (Day 1 measured at afternoon, evening and night and Days 2 through 4 measured at morning, afternoon, evening and night). This is averaged over 16 assessment points for Cycle 2 (Days 1 through 4 measured at morning, afternoon, evening and night).

  Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4)

• Average Nausea Defined as the [AVERAGE] Nausea Rating Across 15 Assessment Points at Cycle 1 and 16 Assessment Points at Cycle 2 (Comparing Prochlorperazine or Olanzapine to Control Arm)

  Will be measured on a 7-point scale ("1: not at all nauseated", "4: moderately nauseated", "7: extremely nauseated"). Higher score is a worse outcome. This is averaged over 15 assessment points for Cycle 1 (Day 1 measured at afternoon, evening and night and Days 2 through 4 measured at morning, afternoon, evening and night). This is averaged over 16 assessment points for Cycle 2 (Days 1 through 4 measured at morning, afternoon, evening and night).

  Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4)

Secondary Outcomes (2)

• The Secondary Outcome Variable Will be [ MAXIMUM ] Nausea (Measured on a 7-point Scale Anchored by ("1:Not at All Nauseated" and 7:"Extremely Nauseated"). Difference of Average Nausea Between Control and Experimental Arms Will be Calculated and Compared.

  Nausea measured at Cycle 1 Chemotherapy (15 time points which is Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (16 time points which is Days 1,2,3,4)

• Vomiting (Yes/No) at Cycle 2 in Participants Who Experienced CINV at Cycle 1.

  Vomiting measured at Cycle 1 Chemotherapy (Yes/No on Days 1,2,3,4) and also measured at Cycle 2 Chemotherapy (Yes/No on Days 1,2,3,4)

Other Outcomes (4)

• Regimens: Chemotherapy Regimens at Cycle 2

  Cycle 2 Chemotherapy

• Emetogenic Potential

  Cycle 2 Chemotherapy

• Vomiting at Cycle 1 of Chemotherapy

  Cycle 1 Chemotherapy

Study Arms (3)

Group I (netupitant/palonosetron hydrochloride, dexamethasone

EXPERIMENTAL

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.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Netupitant/Palonosetron Hydrochloride; Other: Placebo; Other: Quality-of-Life Assessment

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

EXPERIMENTAL

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.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Netupitant/Palonosetron Hydrochloride; Other: Placebo; Drug: Prochlorperazine; Other: Quality-of-Life Assessment

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

EXPERIMENTAL

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.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Netupitant/Palonosetron Hydrochloride; Drug: Olanzapine; Other: Placebo; Other: Quality-of-Life Assessment

Interventions

Dexamethasone DRUG

Given PO

Also known as: 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

Group I (netupitant/palonosetron hydrochloride, dexamethasone; Group II (net/pal hydro, dexa, prochlorperazine, placebo); Group III (net/pal hydro, dexa, olanzapine, placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Group I (netupitant/palonosetron hydrochloride, dexamethasone; Group II (net/pal hydro, dexa, prochlorperazine, placebo); Group III (net/pal hydro, dexa, olanzapine, placebo)

Netupitant/Palonosetron Hydrochloride DRUG

Given PO

Also known as: Akynzeo

Group I (netupitant/palonosetron hydrochloride, dexamethasone; Group II (net/pal hydro, dexa, prochlorperazine, placebo); Group III (net/pal hydro, dexa, olanzapine, placebo)

Olanzapine DRUG

Given PO

Also known as: LY 170053, Zydis, Zyprexa, Zyprexa Zydis

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

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Group I (netupitant/palonosetron hydrochloride, dexamethasone; Group II (net/pal hydro, dexa, prochlorperazine, placebo); Group III (net/pal hydro, dexa, olanzapine, placebo)

Prochlorperazine DRUG

Given PO

Also known as: RP 6140, SKF-4657

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

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Group I (netupitant/palonosetron hydrochloride, dexamethasone; Group II (net/pal hydro, dexa, prochlorperazine, placebo); Group III (net/pal hydro, dexa, olanzapine, placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rochester NCORP Research Base: lead
• National Cancer Institute (NCI): collaborator

Study Sites (18)

Hawaii MU NCORP

Honolulu, Hawaii, 96813, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Gulf South MU-NCORP

New Orleans, Louisiana, 70112, United States

Location

Michigan Cancer Research Consortium

Ann Arbor, Michigan, 48106, United States

Location

Cancer Research Consortium of West Michigan

Grand Rapids, Michigan, 49503, United States

Location

Health Partners Inc

Minneapolis, Minnesota, 55454, United States

Location

Cancer Research for the Ozarks NCORP

Springfield, Missouri, 65804, United States

Location

Nevada Cancer Research Foundation NCORP

Las Vegas, Nevada, 89106, United States

Location

University of Rochester NCORP Research Base

Rochester, New York, 14642, United States

Location

Southeast Clinical Oncology Research Program

Winston-Salem, North Carolina, 27104, United States

Location

Columbus NCORP

Columbus, Ohio, 43215, United States

Location

Dayton Clinical Oncology Program

Dayton, Ohio, 45459, United States

Location

Geisinger Cancer Institute NCORP

Danville, Pennsylvania, 17822, United States

Location

Greenville NCORP

Greenville, South Carolina, 29615, United States

Location

Upstate Carolina NCORP

Spartanburg, South Carolina, 29303, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Gundersen Health System

La Crosse, Wisconsin, 54601, United States

Location

Aurora NCORP

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; netupitant; Palonosetron; netupitant, palosentron drug combination; Olanzapine; Prochlorperazine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines; Phenothiazines; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Luke J. Peppone, PhD, MPH
• Organization: University of Rochester Medical Center

Luke_Peppone@urmc.rochester.edu

585-275-7827

Study Officials

• Luke Peppone

  University of Rochester NCORP Research Base

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery and Orthopaedics

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 8, 2017
• Study Start: April 19, 2018
• Primary Completion: April 13, 2024
• Study Completion: April 13, 2024
• Last Updated: September 25, 2025
• Results First Posted: September 25, 2025

Record last verified: 2025-09

Locations

US (18)