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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00343460
• Other study ID #: CDR0000489413
• Secondary ID: APP-C2006-01
• Status: Completed
• Phase: Phase 3
• First received: June 22, 2006
• Last updated: November 5, 2013
• Start date: April 2006
• Est. completion date: May 2009

Study information

• Verified date: August 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1338
• Est. completion date: May 2009
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Nausea
• Nausea and Vomiting
• Unspecified Adult Solid Tumor, Protocol Specific
• Vomiting

Intervention

Drug:
• APF530
Given subcutanously
• dexamethasone
Given IV and orally
• palonosetron hydrochloride
Given IV

Other:
• placebo
Given subcutanously or IV

Locations

Country	Name	City	State
United States	Cancer Outreach Associates - Abingdon	Abingdon	Virginia
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Pacific Cancer Medical Center, Incorporated	Anaheim	California
United States	Anniston Oncology, PC	Anniston	Alabama
United States	Mercy Medical Center	Baltimore	Maryland
United States	Julie and Ben Rogers Cancer Institute at Memorial Hermann Baptist Beaumont Hospital	Beaumont	Texas
United States	Center for Cancer and Blood Disorders at Suburban Hospital	Bethesda	Maryland
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Southbay Oncology / Hematology Medical Group	Campbell	California
United States	Gabrail Cancer Center - Canton Office	Canton	Ohio
United States	Charleston Hematology Oncology Associates, PA	Charleston	South Carolina
United States	Columbus Clinic, PC	Columbus	Georgia
United States	Compassionate Cancer Care Medical Group Incorporated - Corona	Corona	California
United States	Gabrail Cancer Center - Dover Office	Dover	Ohio
United States	Falck Cancer Center at Arnot Ogden Medical Center	Elmira	New York
United States	Compassionate Cancer Care Medical Group Incorporated - Fountain Valley	Fountain Valley	California
United States	Palo Verde Hematology Oncology - Glendale	Glendale	Arizona
United States	Center for Clinical Research at Washington County Hospital	Hagerstown	Maryland
United States	Kentucky Cancer Clinic - Hazard	Hazard	Kentucky
United States	Comprehensive Cancer Center at Pardee Hospital	Hendersonville	North Carolina
United States	Investigative Clinical Research, LLC	Indianapolis	Indiana
United States	Kansas City Cancer Centers - South	Kansas City	Missouri
United States	Western Washington Oncology, Incorporated, PS at Western Washington Cancer Center	Lacey	Washington
United States	Hematology-Medical Oncology Associates at Central Maine Comprehensive Cancer Center	Lewiston	Maine
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Advanced Research Management Services, Incorporated	Los Angeles	California
United States	Kenmar Research Institute	Los Angeles	California
United States	Kentuckiana Cancer Institute, PLLC	Louisville	Kentucky
United States	MedCentral - Mansfield Hospital	Mansfield	Ohio
United States	Signal Point Hematology Oncology Incorporated	Middletown	Ohio
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Cancer Center of Indiana	New Albany	Indiana
United States	Pasco Pinellas Cancer Center - New Port Richey	New Port Richey	Florida
United States	Innovative Medical Research of South Florida, Incorporated	North Miami Beach	Florida
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Medical Oncology Care Associates - Orange	Orange	California
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Northern Michigan Hospital	Petoskey	Michigan
United States	Star Hematology & Oncology	Phillipsburg	New Jersey
United States	Pottsville Cancer Clinic	Pottsville	Pennsylvania
United States	Hudson Valley Hematology-Oncology Associates - Poughkeepsie	Poughkeepsie	New York
United States	Virginia Oncology Care, PC	Richlands	Virginia
United States	Boice Willis Clinic, PA	Rocky Mount	North Carolina
United States	Eastern North Carolina Medical Group, PLLC	Rocky Mount	North Carolina
United States	Texas Cancer Clinic	San Antonio	Texas
United States	Clintell, Incorporated	Skokie	Illinois
United States	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington
United States	Arizona Clinical Research Center, Incorporated	Tucson	Arizona
United States	Cancer Treatment Centers of America at Southwestern Regional Medical Center	Tulsa	Oklahoma
United States	Family Medicine of Vincennes Clinical Trial Center	Vincennes	Indiana
United States	Medical Center Vincennes	Vincennes	Indiana
United States	Providence Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Heron Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with complete response (CR) during acute phase (0-24 hours) after administration of chemotherapy course 1			No
Primary	Proportion of patients with CR during delayed-onset phase (24-120 hours) after administration of chemotherapy course 1			No
Secondary	Proportion of patients with complete control during the acute phase, delayed-onset phase, and during chemotherapy course 1 (0-120 hours)			No
Secondary	Proportion of patients with total response during the acute phase, delayed-onset phase, and during chemotherapy course 1			No
Secondary	Proportion of patients with major, minor, or failure of emesis control during the acute phase, delayed-onset phase, and during chemotherapy course 1			No
Secondary	Number of emetic episodes during the acute and delayed-onset phase			No
Secondary	Time to treatment failure based on time to first emetic episode or time to first use of rescue medication			No
Secondary	First and overall use of rescue medication			No
Secondary	Severity of nausea daily and during chemotherapy course 1 (0-120 hours)			No
Secondary	Sustainability of antiemetic effect of APF530 over multiple chemotherapy courses			No
Secondary	Quality of life and the impact of nausea and vomiting on day 5			No
Secondary	Patient's global satisfaction with antiemetic therapy during acute phase and chemotherapy course 1			No