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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00343460

Enrollment

1428

Registered

2006-06-23

Start date

2006-06-01

Completion date

2009-02-01

Last updated

2026-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nausea and Vomiting, Unspecified Adult Solid Tumor, Protocol Specific

Keywords

nausea and vomiting, unspecified adult solid tumor, protocol specific

Brief summary

This randomized phase III trial is studying APF530 and dexamethasone to see how well they work compared with palonosetron and dexamethasone in preventing nausea and vomiting in patients receiving chemotherapy for cancer.

Detailed description

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.

Interventions

DRUGAPF530

Given subcutanously

DRUGdexamethasone

Given IV and orally

DRUGPalonosetron Hydrochloride

Given IV

OTHERplacebo

Given subcutanously or IV

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 120 Years

Healthy volunteers

Inclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Patients With Complete Response (CR) During Acute Phase (0-24 Hours) After Administration of Chemotherapy Course 1	0-24 Hours	Complete Response is defined as no emetic episodes and no use of rescue medications
Proportion of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1	24-120 Hours	Complete Response is defined as no emetic episodes and no use of rescue medications

Secondary

Measure	Time frame	Description
Proportion of Patients With Complete Control During the Acute Phase (0-24 Hours), Delayed-onset Phase (24-120 Hours), and During Chemotherapy Course 1	0-120 Hours	Complete control is defined as complete response with no more than mild nausea.
Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 1	0-120 Hours	TR during acute phase is defined as Complete Response with no nausea during 0 to 24 hours following the administration of chemotherapy in Cycle 1. TR during delayed-onset phase is defined as Complete Response with no nausea during \>24 to 120 hours following the administration of chemotherapy in Cycle 1. TR during overall risk period is defined as Complete Response with no nausea during 0 to 120 hours following the administration of chemotherapy in Cycle 1.
Number of Emetic Episodes	Days 1-5	Number of Emetic Episodes - days 1-5
Time to First Treatment Failure	0-120 Hours	Proportions of subjects event free at 24, 48, 72, 96, and 120 hours after chemotherapy administration
First and Overall Use of Rescue Medication	0-120 Hours	—
Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours)	0-120 Hours	Maximum severity of nausea, days 1-5
Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses	0-120 Hours	Sustainability of Overall Complete Response (CR 0-120 hrs) Over Two, Three, and Four Cycles Complete Response is defined as no emetic episodes and no use of rescue medications
Quality of Life and the Impact of Nausea and Vomiting on Day 5	5 days	Functional Living Index
Patient's Global Satisfaction With Antiemetic Therapy During Acute Phase and Chemotherapy Course 1	0- 24 Hours	Subject who were very satisfied on Day 1

Countries

United States

Contacts

STUDY_CHAIRJohn Barr, PhD

Heron Therapeutics

Participant flow

Participants by arm

Arm	Count
Cycle 1 APF530 5 mg - Moderately Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	214
Cycle 1 APF530 10 mg - Moderately Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	212
Cycle 1 Aloxi 0.25 mg - Moderately Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	208
Cycle 1 APF530 5 mg - Highly Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	229
Cycle 1 APF530 10 mg - Highly Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	240
Cycle 1 Aloxi 0.25 Highly Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	238
Total	1,341

Baseline characteristics

Characteristic	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 Highly	Total
Age, Continuous	54.8 years STANDARD_DEVIATION 12.8	55.1 years STANDARD_DEVIATION 12.79	57.3 years STANDARD_DEVIATION 12.36	57.6 years STANDARD_DEVIATION 13.35	56.8 years STANDARD_DEVIATION 13.2	58.1 years STANDARD_DEVIATION 13.74	56.62 years STANDARD_DEVIATION 13.04
Sex: Female, Male Female	189 Participants	177 Participants	177 Participants	153 Participants	152 Participants	158 Participants	1006 Participants
Sex: Female, Male Male	25 Participants	35 Participants	31 Participants	76 Participants	88 Participants	80 Participants	335 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
other Total, other adverse events	335 / 464	349 / 468	313 / 472	422 / 528	413 / 515
serious Total, serious adverse events	42 / 464	36 / 468	27 / 472	61 / 528	73 / 515

Outcome results

Primary