APF530 or Palonosetron Combined With Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Cancer - Full Text View

Sponsor:	A.P. Pharma, Inc.
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00343460

Purpose

RATIONALE: Antiemetic drugs, such as APF530, palonosetron, and dexamethasone, may help lessen or prevent nausea and vomiting in patients receiving chemotherapy for cancer. It is not yet known whether APF530 is more effective than palonosetron when given together with dexamethasone in preventing nausea and vomiting caused by chemotherapy.

PURPOSE: 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.

Condition	Intervention	Phase
Nausea and Vomiting Unspecified Adult Solid Tumor, Protocol Specific	Drug: APF530 Drug: dexamethasone Drug: palonosetron hydrochloride Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Double-Blind Primary Purpose: Supportive Care
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Nausea and Vomiting

Drug Information available for: Dexamethasone Dexamethasone acetate Doxiproct plus Granisetron hydrochloride Granisetron RS 25233-197 Palonosetron Hydrochloride Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Proportion of patients with complete response (CR) during acute phase (0-24 hours) after administration of chemotherapy course 1 [ Designated as safety issue: No ]
Proportion of patients with CR during delayed-onset phase (24-120 hours) after administration of chemotherapy course 1 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients with complete control during the acute phase, delayed-onset phase, and during chemotherapy course 1 (0-120 hours) [ Designated as safety issue: No ]
Proportion of patients with total response during the acute phase, delayed-onset phase, and during chemotherapy course 1 [ Designated as safety issue: No ]
Proportion of patients with major, minor, or failure of emesis control during the acute phase, delayed-onset phase, and during chemotherapy course 1 [ Designated as safety issue: No ]
Number of emetic episodes during the acute and delayed-onset phase [ Designated as safety issue: No ]
Time to treatment failure based on time to first emetic episode or time to first use of rescue medication [ Designated as safety issue: No ]
First and overall use of rescue medication [ Designated as safety issue: No ]
Severity of nausea daily and during chemotherapy course 1 (0-120 hours) [ Designated as safety issue: No ]
Sustainability of antiemetic effect of APF530 over multiple chemotherapy courses [ Designated as safety issue: No ]
Quality of life and the impact of nausea and vomiting on day 5 [ Designated as safety issue: No ]
Patient's global satisfaction with antiemetic therapy during acute phase and chemotherapy course 1 [ Designated as safety issue: No ]

Estimated Enrollment:	1338
Study Start Date:	April 2006
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 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.	Drug: dexamethasone Given IV and orally Drug: palonosetron hydrochloride Given IV Other: placebo Given subcutanously or IV
Experimental: 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.	Drug: APF530 Given subcutanously Drug: dexamethasone Given IV and orally Other: placebo Given subcutanously or IV
Experimental: 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.	Drug: APF530 Given subcutanously Drug: dexamethasone Given IV and orally Other: placebo Given subcutanously or IV

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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00343460

Show 52 Study Locations

Sponsors and Collaborators

A.P. Pharma, Inc.

Investigators

Study Chair:

John Barr, PhD

A.P. Pharma, Inc.

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00343460 History of Changes
Other Study ID Numbers:	CDR0000489413, APP-C2006-01
Study First Received:	June 22, 2006
Last Updated:	May 8, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

nausea and vomiting
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Nausea
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Dexamethasone acetate
Dexamethasone
Granisetron
Dexamethasone 21-phosphate
BB 1101
Palonosetron
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on February 09, 2012