Granisetron, Dexamethasone, Prochlorperazine, Aprepitant, and Palonosetron in Preventing Nausea in Women Undergoing Chemotherapy for Breast Cancer

Condition(s) targeted: Breast Cancer; Nausea and Vomiting

Intervention: aprepitant (Drug); dexamethasone (Drug); granisetron hydrochloride (Drug); palonosetron hydrochloride (Drug); placebo (Drug); prochlorperazine (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Rochester

Official(s) and/or principal investigator(s):
Joseph A. Roscoe, PhD, Principal Investigator, Affiliation: James P. Wilmot Cancer Center

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 women undergoing chemotherapy for breast cancer.

Official title: Prevention of Delayed Nausea A Phase III Double-Blind Placebo-Controlled Clinical Trial

Study design: Supportive Care, Randomized, Double-Blind, Placebo Control

Primary outcome:

Severity of delayed nausea

Interference with functioning caused by nausea or emesis

Secondary outcome: Change in quality of life score between pre- and post-treatment measurements

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 anthracycline 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 anthracycline 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)

- Correlate sleep quality, physical exercise, and fatigue with chemotherapy-induced nausea

in these patients.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to CCOP center. 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

DISEASE CHARACTERISTICS:

- Diagnosis of breast cancer

- Chemotherapy-naive disease

- Must be scheduled to receive a chemotherapy treatment containing doxorubicin

hydrochloride or epirubicin hydrochloride (any dose or schedule) without concurrent radiotherapy or interferon treatment

- Chemotherapy may be for adjuvant, neoadjuvant, curative, or palliative intent

- Dose-dense regimens allowed (e. g., doxorubicin hydrochloride or epirubicin

hydrochloride given every 2 weeks)

- No multiple-day doses of doxorubicin hydrochloride or epirubicin

hydrochloride

- No symptomatic brain metastases

- Hormone receptor status not specified

PATIENT CHARACTERISTICS:

- Female

- Menopausal status not specified

- No concurrent or impending bowel obstruction

- Able to understand English

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No concurrent pimozide, terfenadine, astemizole, or cisapride

- No concurrent doxorubicin hydrochloride liposome or cisplatin

- No concurrent multiple-day doses of dacarbazine, altretamine, nitrosoureas, or

streptozocin

- Multiple-day doses of other chemotherapy agents allowed

CCOP - Central Illinois, Decatur, Illinois 62526, United States; Recruiting
James L. Wade, MD, Phone: 217-876-6618, Email: peggyv@dmhhs.org

CCOP - Wichita, Wichita, Kansas 67214-3882, United States; Recruiting
Shaker R. Dakhil, MD, FACP, Phone: 316-268-5784, Email: marge_good@via-christi.org

CCOP - Grand Rapids, Grand Rapids, Michigan 49503, United States; Recruiting
Marianne K. Lange, MD, Phone: 616-391-1230, Email: connie.szczepanek@grcop.org

CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States; Recruiting
Raymond S. Lord, MD, Phone: 269-373-7458, Email: rlord@wmcc.org

CCOP - Metro-Minnesota, St. Louis Park, Minnesota 55416, United States; Recruiting
Patrick J. Flynn, MD, Phone: 952-993-1576, Email: hillre@parknicollet.com

CCOP - Kansas City, Kansas City, Missouri 64131, United States; Recruiting
Rakesh Gaur, MD, Phone: 816-823-0555, Email: leslie.herst@hcamidwest.com

CCOP - Hematology-Oncology Associates of Central New York, East Syracuse, New York 13057, United States; Recruiting
Jeffrey J. Kirshner, MD, Phone: 315-472-7504, Email: csweeney@hoacny.com

CCOP - North Shore University Hospital, Manhassett, New York 11030, United States; Recruiting
Vincent P. Vinciguerra, MD, Phone: 516-734-8918, Email: nnier@nshs.edu

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Joseph A. Roscoe, PhD, Phone: 585-275-5513

CCOP - Southeast Cancer Control Consortium, Goldsboro, North Carolina 27534-9479, United States; Recruiting
James N. Atkins, MD, Phone: 336-777-3036, Email: rburgess@wfubmc.edu

CCOP - Columbus, Columbus, Ohio 43215, United States; Recruiting
J. Philip Kuebler, MD, PhD, Phone: 614-488-2647, Email: debby@mail.columbus-ccop.org

CCOP - Dayton, Dayton, Ohio 45429, United States; Recruiting
Howard M. Gross, MD, Phone: 937-395-8679, Email: bernadette.bensman@wright.edu

CCOP - Greenville, Greenville, South Carolina 29615, United States; Recruiting
Jeffrey K. Giguere, MD, FACP, Phone: 864-241-6251, Email: lyndon.evans@usoncology.com

CCOP - Northwest, Tacoma, Washington 98405-0986, United States; Recruiting
Lauren K. Colman, MD, Phone: 253-403-1461, Email: karyn.hart@multicare.org

CCOP - Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, United States; Recruiting
Tarit K. Banerjee, MD, FACP, Phone: 715-389-5592, Email: banerjee.tarit@marshfieldclinic.org

Clinical trial summary from the National Cancer Institute's PDQ® database

Featured trial article

Starting date: December 2006
Last updated: October 23, 2008