Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial - Full Text View

Purpose

RATIONALE: Antiemetic drugs, such as granisetron, dexamethasone, prochlorperazine, aprepitant, and palonosetron, may help lessen or prevent nausea. It is not yet known which combination of antiemetic drugs is more effective in preventing nausea caused by chemotherapy.

PURPOSE: This randomized phase III trial is comparing different combinations of granisetron, dexamethasone, prochlorperazine, aprepitant, and palonosetron to see how well they work in preventing nausea in patients undergoing chemotherapy for breast cancer.

Condition	Intervention	Phase
Nausea	Drug: aprepitant Drug: dexamethasone Drug: granisetron hydrochloride Drug: palonosetron hydrochloride Drug: prochlorperazine Drug: placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Supportive Care
Official Title:	Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: Dexamethasone Prochlorperazine Prochlorperazine maleate Prochlorperazine edisylate Dexamethasone sodium phosphate Dexamethasone acetate Granisetron hydrochloride Granisetron Palonosetron Palonosetron hydrochloride Aprepitant Fosaprepitant Fosaprepitant dimeglumine

Genetic and Rare Diseases Information Center resources: Inflammatory Breast Cancer Breast Cancer, Male

U.S. FDA Resources

Further study details as provided by University of Rochester:

Primary Outcome Measures:

Home Record: Severity of Delayed Nausea [ Time Frame: average of day 1 afternoon, evening and night, and all of days 2 and 3 ] [ Designated as safety issue: No ]
1=not at all nauseated to 7=extremely nauseated, therefore higher values are worse


Enrollment:	1021
Study Start Date:	December 2006
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.	Drug: dexamethasone Given orally or IV Other Name: Decadron Drug: palonosetron hydrochloride Given orally or IV Other Name: Aloxi Drug: prochlorperazine Given orally or IV Other Name: Compazine Drug: placebo Given orally
Experimental: Arm II Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.	Drug: dexamethasone Given orally or IV Other Name: Decadron Drug: granisetron hydrochloride Given orally or IV Other Name: Kytril Drug: prochlorperazine Given orally or IV Other Name: Compazine Drug: placebo Given orally
Active Comparator: Arm III Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3.	Drug: aprepitant Given orally or IV Other Name: Emend Drug: dexamethasone Given orally or IV Other Name: Decadron Drug: palonosetron hydrochloride Given orally or IV Other Name: Aloxi Drug: placebo Given orally
Experimental: Arm IV Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3.	Drug: dexamethasone Given orally or IV Other Name: Decadron Drug: palonosetron hydrochloride Given orally or IV Other Name: Aloxi Drug: prochlorperazine Given orally or IV Other Name: Compazine Drug: placebo Given orally

Detailed Description:

OBJECTIVES:

Primary

Compare the efficacy of palonosetron hydrochloride and dexamethasone followed by prochlorperazine with vs without dexamethasone in preventing delayed nausea in women with chemotherapy-naive breast cancer. (Arms I and IV)
Determine if palonosetron hydrochloride is more effective than granisetron hydrochloride in controlling treatment-related delayed nausea in these patients. (Arms I and II)
Determine if the currently recommended antiemetic guideline of aprepitant combined with palonosetron hydrochloride and dexamethasone is the most effective antiemetic regimen for controlling treatment-related delayed nausea in these patients. (Arms III and IV)

Secondary

Determine if the addition of dexamethasone to prochlorperazine is more effective than the same regimen without dexamethasone for reducing interference with functioning caused by chemotherapy-induced nausea and vomiting in these patients. (Arms I and IV)
Determine if palonosetron hydrochloride is more effective than granisetron hydrochloride for reducing interference with functioning caused by chemotherapy-induced nausea and vomiting in these patients. (Arms I and II)
Determine if the currently recommended antiemetic guideline of aprepitant combined with palonosetron hydrochloride and dexamethasone is the most effective antiemetic regimen for reducing interference with functioning due to chemotherapy-induced nausea and vomiting in these patients. (Arms III and IV)

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to CCOP center and gender. Patients are randomized to 1 of 4 treatment arms. Patients receive study treatment approximately 30 minutes before their scheduled first chemotherapy treatment.

Arm I: Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.
Arm II: Patients receive granisetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and another oral placebo once daily on days 2 and 3.
Arm III: Patients receive palonosetron hydrochloride IV and dexamethasone IV once on day 1, oral aprepitant once daily on days 1-3, and oral dexamethasone once daily and oral placebo twice daily on days 2 and 3.
Arm IV: Patients receive palonosetron hydrochloride IV, dexamethasone IV, and oral placebo once on day 1 and oral prochlorperazine 3 times daily and oral dexamethasone once daily on days 2 and 3.

Quality of life is assessed at baseline and on day 4. Nausea and vomiting, fatigue, sleep quality, exercise, and the need for rescue medication (metoclopramide) are assessed on days 1-4.

PROJECTED ACCRUAL: A total of 890 patients will be accrued for this study.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Have a diagnosis of cancer and be chemotherapy naive.
Must be scheduled to receive a chemotherapy treatment containing doxorubicin hydrochloride, epirubicin hydrochloride, cisplatin, carboplatin, or oxaliplatin (any dose or schedule) without concurrent radiotherapy or interferon treatment
Chemotherapy may be for adjuvant, neoadjuvant, curative or palliative intent.
Dose-dense regimens (e.g. chemotherapy with doxorubicin or epirubicin given every two weeks)are allowed.
For the purposes of this study, Day 1 of chemotherapy will be defined as the day of administration of cisplatin, carboplatin, oxaliplatin, doxorubicin or epirubicin.
Regimens with multiple-day doses of doxorubicin, epirubicin, cisplatin, carboplatin, oxaliplatin, dacarbazine, hexamethylmelamine, nitrosoureas, or streptozocin are not allowed. Chemotherapy agents, other than those listed above, may be given orally, intravenously, or by continuous infusion on one or multiple days.
Able to understand English

Exclusion criteria:

No symptomatic brain metastases
No concurrent or impending bowel obstruction
Regimens containing liposomal doxorubicin or cisplatin are not allowed.
No concurrent pimozide, terfenadine, astemizole, or cisapride
No concurrent doxorubicin hydrochloride liposome or cisplatin
No concurrent multiple-day doses of dacarbazine, altretamine, nitrosoureas, streptozocin, cisplatin, carboplatin, or oxaliplatin

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00475085

Locations


United States, Alabama
MBCCOP - Gulf Coast
Mobile, Alabama, United States, 36695
United States, Illinois
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Michigan
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-3731
United States, Minnesota
CCOP - Metro-Minnesota
St. Louis Park, Minnesota, United States, 55416
United States, Missouri
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New York
CCOP - Hematology-Oncology Associates of Central New York
East Syracuse, New York, United States, 13057
CCOP - North Shore University Hospital
Manhassett, New York, United States, 11030
United States, North Carolina
CCOP - Southeast Cancer Control Consortium
Goldsboro, North Carolina, United States, 27534-9479
United States, Ohio
CCOP - Columbus
Columbus, Ohio, United States, 43215
CCOP - Dayton
Dayton, Ohio, United States, 45429
United States, South Carolina
CCOP - Greenville
Greenville, South Carolina, United States, 29615
United States, Washington
CCOP - Northwest
Tacoma, Washington, United States, 98405-0986
United States, Wisconsin
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449

Sponsors and Collaborators

Joseph Roscoe

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Joseph A. Roscoe, PhD	James P. Wilmot Cancer Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Roscoe JA, Heckler CE, Morrow GR, Mohile SG, Dakhil SR, Wade JL, Kuebler JP. Prevention of delayed nausea: a University of Rochester Cancer Center Community Clinical Oncology Program study of patients receiving chemotherapy. J Clin Oncol. 2012 Sep 20;30(27):3389-95. doi: 10.1200/JCO.2011.39.8123. Epub 2012 Aug 20.


Responsible Party:	Joseph Roscoe, Research Associate Professor, University of Rochester NCORP Research Base
ClinicalTrials.gov Identifier:	NCT00475085 History of Changes
Other Study ID Numbers:	CDR0000544841 U10CA037420 URCC-U1105
Study First Received:	May 16, 2007
Results First Received:	July 12, 2013
Last Updated:	October 13, 2015
Health Authority:	United States: Federal Government

Keywords provided by University of Rochester:


nausea and vomiting recurrent breast cancer stage I breast cancer stage II breast cancer stage IIIA breast cancer	stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer inflammatory breast cancer male breast cancer

Additional relevant MeSH terms:


Nausea Signs and Symptoms, Digestive Signs and Symptoms Dexamethasone acetate Dexamethasone Aprepitant Fosaprepitant Prochlorperazine Granisetron Dexamethasone 21-phosphate BB 1101 Palonosetron Anti-Inflammatory Agents Antiemetics Autonomic Agents	Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Neurokinin-1 Receptor Antagonists Neurotransmitter Agents Antipsychotic Agents Tranquilizing Agents

Nausea
Signs and Symptoms, Digestive
Signs and Symptoms
Dexamethasone acetate
Dexamethasone
Aprepitant
Fosaprepitant
Prochlorperazine
Granisetron
Dexamethasone 21-phosphate
BB 1101
Palonosetron
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Antipsychotic Agents
Tranquilizing Agents

ClinicalTrials.gov processed this record on September 26, 2016