Clinical trial NCT02116530: Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy
Official title: Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting (CINV) in Patients Receiving Highly Emetogenic Chemotherapy (HEC): A Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hematopoietic/Lymphoid Cancer
Nausea and Vomiting
Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-04-17
Enrollment: 401
Sex: ALL
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 antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. Olanzapine may help prevent chemotherapy-induced nausea and vomiting by blocking brain receptors that appear to be involved in nausea and vomiting.

Detailed description: Patients with cancer may receive chemotherapy that may cause nausea and vomiting. The purpose of this study is to determine if the use of olanzapine in combination with antiemetic therapy can significantly reduce nausea and vomiting in a large number of patients receiving chemotherapy. Patients are randomized to one of two treatment arms. Please see the "Arms and Intervention" sections for more detailed information. The primary objective is to compare the number of patients with no nausea for the acute (0-24 hours post-chemotherapy), delayed (24-120 hours post-chemotherapy) and overall periods (0-120 hours post-chemotherapy) for patients receiving HEC. The secondary objectives are:

1. To compare the complete response (CR) (no emetic episodes and no use of rescue medication) in the acute, delayed and overall periods
2. To compare the incidences of potential toxicities ascribed to olanzapine

Protocol treatment is to begin ≤ 14 days of registration. Patients will receive treatment on Days 1-4. Patients will be permitted to take rescue therapy of the treating investigator's choice for nausea and/or emesis/retching, based on clinical circumstances. After completing treatment, patients will be monitored for side effects.

Eligibility criteria: * Diagnosis of malignant disease
* No prior chemotherapy and scheduled to receive HEC (either cisplatin-containing regimen or anthracycline + cyclophosphamide \[AC\])

  * Cisplatin at a dose of ≥70mg/m\^2, with or without other chemotherapy agent(s) OR
  * Anthracycline (60 mg/m\^2) plus cyclophosphamide(600 mg/m\^2)
* Age ≥18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
* Required Initial Laboratory Values ≤ 120 days prior to registration

  * Serum Creatinine ≤2.0 mg/dL
  * Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic oxaloacetic transaminase (SGPT) ≤3 x Upper Limit of Normal (ULN)
  * Absolute neutrophil count (ANC) ≥1500/mm\^3
* No nausea or vomiting ≤ 24 hours prior to registration
* Negative pregnancy test (serum or urine) done ≤7 days prior to registration, for women of childbearing potential only (per clinician discretion)
* No severe cognitive compromise
* No known history of CNS disease (e.g. brain metastases, seizure disorder)
* No treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone ≤30 days prior to registration or planned during protocol therapy
* No chronic phenothiazine administration as an antipsychotic agent (patients may receive prochlorperazine and other phenothiazines as rescue anti-emetic therapy)
* No concurrent use of amifostine
* No concurrent abdominal radiotherapy
* No concurrent use of quinolone antibiotic therapy
* No chronic alcoholism (as determined by the investigator)
* No known hypersensitivity to olanzapine
* No known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the previous six months.
* No history of uncontrolled diabetes mellitus (e.g. on insulin or an oral hypoglycemic agent)

Primary outcomes:
measure: Proportion of Patients With no Nausea
timeFrame: 0 to 120 hours after chemotherapy
Secondary outcomes:
measure: Median Nausea Scores
timeFrame: Baseline and Day 2 to Day 6 after chemotherapy
measure: Proportion of Patients With Complete Response
timeFrame: 0 to 120 hours after chemotherapy
measure: Mean Scores of Potential Toxicities Related to Olanzapine as Measured by the Nausea and Vomiting Daily Diary/Questionnaire
timeFrame: Baseline and day 2 to 6 days after chemotherapy
measure: Frequency of Rescue Medication
timeFrame: Day 2 to Day 6 after chemotherapy
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Anchorage Associates in Radiation Medicine
state: Alaska
city: Anchorage
country: United States
facility: Anchorage Radiation Therapy Center
state: Alaska
city: Anchorage
country: United States
facility: Alaska Breast Care and Surgery LLC
state: Alaska
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology LLC
state: Alaska
city: Anchorage
country: United States
facility: Alaska Regional Hospital
state: Alaska
city: Anchorage
country: United States
facility: Alaska Women's Cancer Care
state: Alaska
city: Anchorage
country: United States
facility: Anchorage Oncology Centre
state: Alaska
city: Anchorage
country: United States
facility: Katmai Oncology Group
state: Alaska
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Dublin
country: United States
facility: Epic Care-Dublin
state: California
city: Emeryville
country: United States
facility: Bay Area Breast Surgeons Inc
state: California
city: Emeryville
country: United States
facility: Epic Care Partners in Cancer Care
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Medical Center - Summit Campus
state: California
city: Oakland
country: United States
facility: Bay Area Tumor Institute
state: California
city: Oakland
country: United States
facility: Hematology and Oncology Associates-Oakland
state: California
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers-Aurora
state: Colorado
city: Aurora
country: United States
facility: The Medical Center of Aurora
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers-Boulder
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers-Penrose
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Exempla Saint Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - Saint Lukes Medical Center - Health One
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers-Midtown
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers-Rose
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Durango
country: United States
facility: Mercy Medical Center
state: Colorado
city: Durango
country: United States
facility: Southwest Oncology PC
state: Colorado
city: Englewood
country: United States
facility: Comprehensive Cancer Care and Research Institute of Colorado LLC
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Golden
country: United States
facility: Mountain Blue Cancer Care Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers-Greenwood Village
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers-Lakewood
state: Colorado
city: Lakewood
country: United States
facility: Saint Anthony Hospital
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers-Littleton
state: Colorado
city: Littleton
country: United States
facility: Littleton Adventist Hospital
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers-Sky Ridge
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Longmont United Hospital
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers-Longmont
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Parker
country: United States
facility: Parker Adventist Hospital
state: Colorado
city: Parker
country: United States
facility: Rocky Mountain Cancer Centers-Parker
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Centers - Pueblo
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers-Thornton
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Hartford
country: United States
facility: Saint Francis Hospital and Medical Center
state: Connecticut
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Gynecologic Oncology LLC
state: Delaware
city: Newark
country: United States
facility: Delaware Clinical and Laboratory Physicians PA
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Newark
country: United States
facility: Regional Hematology and Oncology PA
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Sanford
country: United States
facility: Nanticoke Memorial Hospital
state: Delaware
city: Wilmington
country: United States
facility: Christiana Care Health System-Wilmington Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Daytona Beach
country: United States
facility: Florida Hospital Memorial Medical Center
state: Florida
city: Albany
country: United States
facility: Phoebe Putney Memorial Hospital
state: Georgia
city: 'Aiea
country: United States
facility: Oncare Hawaii Inc-Pali Momi
state: Hawaii
city: 'Aiea
country: United States
facility: Pali Momi Medical Center
state: Hawaii
city: 'Ewa Beach
country: United States
facility: The Cancer Center of Hawaii-Leeward
state: Hawaii
city: Honolulu
country: United States
facility: Oncare Hawaii Inc-POB II
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital
state: Hawaii
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Honolulu
country: United States
facility: Kuakini Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Oncare Hawaii Inc-Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii-Liliha
state: Hawaii
city: Honolulu
country: United States
facility: The Cancer Center of Hawaii-Liliha
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Honolulu
country: United States
facility: Tripler Army Medical Center
state: Hawaii
city: Lihue
country: United States
facility: Wilcox Memorial Hospital and Kauai Medical Clinic
state: Hawaii
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Boise
country: United States
facility: Saint Luke's Mountain States Tumor Institute
state: Idaho
city: Fruitland
country: United States
facility: Saint Luke's Mountain States Tumor Institute - Fruitland
state: Idaho
city: Meridian
country: United States
facility: Saint Luke's Mountain States Tumor Institute - Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Luke's Mountain States Tumor Institute - Nampa
state: Idaho
city: Twin Falls
country: United States
facility: Saint Luke's Mountain States Tumor Institute-Twin Falls
state: Idaho
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Carbondale
country: United States
facility: Memorial Hospital of Carbondale
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Elgin
country: United States
facility: Advocate Sherman Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare Galesburg
state: Illinois
city: Galesburg
country: United States
facility: Western Illinois Cancer Treatment Center
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Oconomowoc
country: United States
facility: Oconomowoc Memorial Hospital-ProHealth Care Inc
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Valley Radiation Oncology
state: Illinois
city: Rockford
country: United States
facility: OSF Saint Anthony Medical Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Illinois
city: Mishawaka
country: United States
facility: Memorial Regional Cancer Center Day Road
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Ames
country: United States
facility: Mary Greeley Medical Center
state: Iowa
city: Ames
country: United States
facility: McFarland Clinic PC-William R Bliss Cancer Center
state: Iowa
city: Boone
country: United States
facility: McFarland Clinic PC-Boone
state: Iowa
city: Cedar Rapids
country: United States
facility: Physicians' Clinic of Iowa PC
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates at Mercy Medical Center
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Fort Dodge
country: United States
facility: McFarland Clinic PC-Trinity Cancer Center
state: Iowa
city: Jefferson
country: United States
facility: McFarland Clinic PC-Jefferson
state: Iowa
city: Marshalltown
country: United States
facility: McFarland Clinic PC-Marshalltown
state: Iowa
city: Mason City
country: United States
facility: Mercy Medical Center - North Iowa
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: West Des Moines
country: United States
facility: Methodist West Hospital
state: Iowa
city: Corbin
country: United States
facility: Baptist Health Corbin
state: Kentucky
city: Elizabethtown
country: United States
facility: Hardin Memorial Hospital
state: Kentucky
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Farmington
country: United States
facility: Botsford Hospital
state: Michigan
city: Troy
country: United States
facility: William Beaumont Hospital - Troy
state: Michigan
city: Joplin
country: United States
facility: Mercy Hospital-Joplin
state: Missouri
city: Rolla
country: United States
facility: Mercy Clinic-Rolla-Cancer and Hematology
state: Missouri
city: Rolla
country: United States
facility: Phelps County Regional Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Cancer and Breast Institute-South City
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Clinton
country: United States
facility: Southeastern Medical Oncology Center-Clinton
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center-Goldsboro
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Jacksonville
country: United States
facility: Southeastern Medical Oncology Center-Jacksonville
state: North Carolina
city: Wilson
country: United States
facility: Southeastern Medical Oncology Center-Wilson
state: North Carolina
city: Dayton
country: United States
facility: Dayton NCI Community Oncology Research Program
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital
state: Rhode Island
city: Berlin
country: United States
facility: Central Vermont Medical Center
state: Vermont
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Yelm
country: United States
facility: Providence Regional Cancer System-Yelm
state: Washington
city: Huntington
country: United States
facility: Edwards Comprehensive Cancer Center
state: West Virginia
city: Cheyenne
country: United States
facility: Cheyenne Regional Medical Center-West
state: Wisconsin
city: Chippewa Falls
country: United States
facility: Marshfield Clinic-Chippewa Center
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Center at Sacred Heart
state: Wisconsin
city: Fond Du Lac
country: United States
facility: Saint Agnes Hospital/Agnesian Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology at Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology Limited at Saint Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Mary's Hospital
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Hospital
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Medical Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic-Minocqua Center
state: Wisconsin
city: Mukwonago
country: United States
facility: D N Greenwald Center
state: Wisconsin
city: New Richmond
country: United States
facility: Westfields Hospital/Cancer Center of Western Wisconsin
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology - Oconto Falls
state: Wisconsin
city: Rhinelander
country: United States
facility: Marshfield Clinic at James Beck Cancer Center
state: Wisconsin
city: Rice Lake
country: United States
facility: Lakeview Medical Center-Marshfield Clinic
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic-Rice Lake Center
state: Wisconsin
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Wisconsin
city: Sheboygan
country: United States
facility: Saint Nicholas Hospital
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Clinic Cancer Care at Saint Michael's Hospital
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology - Sturgeon Bay
state: Wisconsin
city: Wausau
country: United States
facility: Marshfield Clinic-Wausau Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Marshfield Clinic - Wisconsin Rapids Center
state: Wisconsin
Study officials:
affiliation: Indiana University School of Medicine South Bend
name: Rudolph M. Navari, MD, PhD, FACP
role: STUDY_CHAIR
References:
citation: Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. doi: 10.1056/NEJMoa1515725.