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

Joseph Roscoe

Status and phase: Completed; Phase 3

Conditions: Nausea

Treatments: Drug: palonosetron hydrochloride; Drug: granisetron hydrochloride; Drug: placebo; Drug: dexamethasone; Drug: prochlorperazine; Drug: aprepitant

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00475085

U10CA037420 (U.S. NIH Grant/Contract)

CDR0000544841

URCC-U1105 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,021 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,021 participants in 4 patient groups

Arm I

Active Comparator group

Description:

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.

Treatment:

Drug: prochlorperazine

Drug: dexamethasone

Drug: placebo

Drug: palonosetron hydrochloride

Arm II

Experimental group

Description:

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.

Treatment:

Drug: prochlorperazine

Drug: dexamethasone

Drug: granisetron hydrochloride

Drug: placebo

Arm III

Active Comparator group

Description:

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.

Treatment:

Drug: aprepitant

Drug: dexamethasone

Drug: placebo

Drug: palonosetron hydrochloride

Arm IV

Experimental group

Description:

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.

Treatment:

Drug: prochlorperazine

Drug: dexamethasone

Drug: placebo

Drug: palonosetron hydrochloride