A Pivotal Phase 3 Observer-Blind, Randomized Clinical Trial of the Efficacy and Safety of APF530 Compared to Aloxi For The Prevention of Acute-Onset and Delayed-Onset Chemotherapy-Induced Nausea and Vomiting Following The Administration of Either Moderately or Highly Emetogenic Chemotherapy Regimens

Trial Information

A Pivotal Phase 3 Observer-Blind, Randomized Clinical Trial of the Efficacy and Safety of APF530 Compared to Aloxi For The Prevention of Acute-Onset and Delayed-Onset Chemotherapy-Induced Nausea and Vomiting Following The Administration of Either Moderately or Highly Emetogenic Chemotherapy Regimens

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.

PROJECTED ACCRUAL: A total of 1,338 patients will be accrued for this study.