APF530 or Aloxi (Palonosetron Hydrochloride) Combined With Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Cancer

OBJECTIVES:

Primary

• Compare the overall activity and effects of APF530 versus palonosetron hydrochloride in combination with dexamethasone for prophylaxis of acute- or delayed-onset, chemotherapy-induced nausea and vomiting in patients undergoing moderately or highly emetogenic chemotherapy for cancer.

Secondary

• Evaluate the safety, tolerability, and efficacy of APF530, in terms of prevention of acute- and delayed-onset nausea and vomiting, in these patients.
• Gather the pharmacokinetics of APF530 in a subset of patients during chemotherapy course 1.
• Gather ECG data (using 24-hour Holter monitoring) in a subset of patients during chemotherapy course 1.

OUTLINE: This is a randomized, placebo-controlled, double-blind, parallel-group, multicenter study. Patients are stratified according to emetogenicity of scheduled chemotherapy (moderate-risk [level 3 or 4] vs high-risk [level 5]). Patients are randomized to 1 of 3 treatment arms (I, II, and III). Patients who are randomized to receive palonosetron hydrochloride during chemotherapy course 1 (arm I) are then re-randomized to 1 of 2 treatment arms (II and III) after chemotherapy course 1 to receive treatment during chemotherapy courses 2-4.

Patients receive palonosetron hydrochloride or APF530 and/or placebo 30-60 minutes before the start of chemotherapy. Patients receive dexamethasone 30-90 minutes before the start of chemotherapy.

• Arm I: Patients receive palonosetron hydrochloride IV, placebo subcutaneously (SC), and dexamethasone IV on day 1 of chemotherapy course 1. Patients in the high-risk (level 5) stratum also receive oral dexamethasone on days 2-4 of all treatment courses.
• Arm II: Patients receive APF530 SC, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.
• Arm III: Patients receive APF530 SC at a higher dose, placebo IV, and dexamethasone IV on day 1 of chemotherapy course 1. Patients then receive APF530 SC (at the same higher dose) and dexamethasone IV on day 1 of chemotherapy courses 2-4. Patients in the high-risk (level 5) stratum also receive oral dexamethasone as in arm I.

A subset of patients undergo blood collection periodically during study for analysis of plasma APF530 concentration.

Quality of life is assessed on day 5 after completion of chemotherapy course 1.

After completion of study treatment, patients are followed at approximately 30 days.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant disease

• No head and neck cancer or upper gastrointestinal cancer
• Scheduled to receive a single day of moderately or highly emetogenic chemotherapy regimen (for ≤ 4 courses)

• Chemotherapy administration ≤ 4 hours
• Duration of each course ≤ 28 days
• Causing nausea and vomiting in 30-100% of patients if untreated according to Hesketh algorithm
• Must be able to receive standardized doses of dexamethasone for the prevention of emesis during study treatment
• No greater than mild nausea or any vomiting within 24 hours before beginning study treatment

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known allergy or hypersensitivity to other selective 5-HT3 receptor antagonists or local anesthetics
• QTc interval ≤ 500 ms
• No cardiac abnormality predisposing the patient to arrhythmia
• No psychological problem that, in the opinion of the investigator, is severe enough to preclude study participation
• No recent history (i.e., ≤ 1 year) of alcohol or drug abuse
• No concurrent condition that, in the opinion of the investigator, could affect assessment of study medication or interfere with the nausea/vomiting response (e.g., severe renal or hepatic impairment)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No radiotherapy 7 days prior to, during, and 5 days after completion of study treatment
• More than 7 days since prior chemotherapy
• More than 7 days since prior and no concurrent prohibited medications (e.g., CYP3A4 inhibitors or other antiemetic medications)
• More than 7 days since prior antinausea medications
• More than 30 days since prior treatment on an investigational trial
• No other concurrent corticosteroids or dexamethasone at a different dose than study treatment
• No concurrent use of APF530, palonosetron hydrochloride, or aprepitant as rescue medications