Clinical trial NCT03367572: Treatment of Refractory Nausea and Vomiting in Patients With Breast Cancer
Official title: Netupitant/Palonosetron Hydrochloride and Dexamethasone With or Without Prochlorperazine or Olanzapine in Improving Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Carcinoma
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-12-08
Enrollment: 1351
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Average nausea defined as the average nausea rating across 15 assessment points (comparing prochlorperazine or olanzapine to control arm)
timeFrame: Up to day 4
Secondary outcomes:
measure: Average nausea defined as the average nausea rating across 15 assessment points (comparing olanzapine to prochlorperazine)
timeFrame: Up to day 4
measure: Presence of any vomiting (yes or no)
timeFrame: Up to day 4
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Hawaii MU NCORP
state: Hawaii
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Gulf South MU-NCORP
state: Louisiana
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer Research Consortium of West Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Health Partners Inc
state: Minnesota
city: Springfield
country: United States
facility: Cancer Research for the Ozarks NCORP
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation NCORP
state: Nevada
city: Rochester
country: United States
facility: University of Rochester NCORP Research Base
state: New York
city: Winston-Salem
country: United States
facility: Southeast Clinical Oncology Research Program
state: North Carolina
city: Columbus
country: United States
facility: Columbus NCORP
state: Ohio
city: Dayton
country: United States
facility: Dayton Clinical Oncology Program
state: Ohio
city: Danville
country: United States
facility: Geisinger Cancer Institute NCORP
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville NCORP
state: South Carolina
city: Spartanburg
country: United States
facility: Upstate Carolina NCORP
state: South Carolina
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center Green Bay
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Health System
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora NCORP
state: Wisconsin
Study officials:
affiliation: University of Rochester NCORP Research Base
name: Luke Peppone
role: PRINCIPAL_INVESTIGATOR
References: