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

Breast Carcinoma Clinical Trial

Official title:

Treatment of Refractory Nausea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03367572
• Other study ID #: URCC16070
• Secondary ID: NCI-2017-00902UR
• Status: Completed
• Phase: Phase 3
• Start date: April 19, 2018
• Est. completion date: February 13, 2024

Study information

• Verified date: April 2024
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1351
• Est. completion date: February 13, 2024
• Est. primary completion date: February 13, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Carcinoma
• Breast Neoplasms

Intervention

Drug:
• Dexamethasone
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Netupitant/Palonosetron Hydrochloride
Given PO
• Olanzapine
Given PO

Other:
• Placebo
Given PO

Drug:
• Prochlorperazine
Given PO

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Columbus NCORP	Columbus	Ohio
United States	Geisinger Cancer Institute NCORP	Danville	Pennsylvania
United States	Dayton Clinical Oncology Program	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Cancer Research Consortium of West Michigan	Grand Rapids	Michigan
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Greenville NCORP	Greenville	South Carolina
United States	Hawaii MU NCORP	Honolulu	Hawaii
United States	Gundersen Health System	La Crosse	Wisconsin
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	Aurora NCORP	Milwaukee	Wisconsin
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Gulf South MU-NCORP	New Orleans	Louisiana
United States	University of Rochester NCORP Research Base	Rochester	New York
United States	Upstate Carolina NCORP	Spartanburg	South Carolina
United States	Cancer Research for the Ozarks NCORP	Springfield	Missouri
United States	Southeast Clinical Oncology Research Program	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of Rochester NCORP Research Base	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

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