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
18 Years
N/A
Both
Nausea and Vomiting, Unspecified Adult Solid Tumor, Protocol Specific
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Outcome Measure:
Proportion of patients with complete response (CR) during acute phase (0-24 hours) after administration of chemotherapy course 1
Safety Issue:
No
Principal Investigator
John Barr, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
A.P. Pharma, Inc.
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000489413
NCT ID:
NCT00343460
Start Date:
April 2006
Completion Date:
Related Keywords:
- Nausea and Vomiting
- Unspecified Adult Solid Tumor, Protocol Specific
- nausea and vomiting
- unspecified adult solid tumor, protocol specific
- Nausea
- Vomiting
Name | Location |
|---|---|
| MultiCare Regional Cancer Center at Tacoma General Hospital | Tacoma, Washington 98405 |
| Veterans Affairs Medical Center - Buffalo | Buffalo, New York 14215 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| McDowell Cancer Center at Akron General Medical Center | Akron, Ohio 44307 |
| Mary Babb Randolph Cancer Center at West Virginia University Hospitals | Morgantown, West Virginia 26506 |
| Northern Michigan Hospital | Petoskey, Michigan 49770 |
| Regional Cancer Center at Singing River Hospital | Pascagoula, Mississippi 39581 |
| Eastern Connecticut Hematology and Oncology Associates | Norwich, Connecticut 06360 |
| MedCentral - Mansfield Hospital | Mansfield, Ohio 44903 |
| Providence Hospital | Washington, District of Columbia 20017 |
| Arizona Clinical Research Center, Incorporated | Tucson, Arizona 85715 |
| Kenmar Research Institute | Los Angeles, California 90057 |
| Mercy Medical Center | Baltimore, Maryland 21202 |
| Kentuckiana Cancer Institute, PLLC | Louisville, Kentucky 40202 |
| Falck Cancer Center at Arnot Ogden Medical Center | Elmira, New York 14905 |
| Pacific Cancer Medical Center, Incorporated | Anaheim, California 92801 |
| Gabrail Cancer Center - Canton Office | Canton, Ohio 44718 |
| Cancer Center of Indiana | New Albany, Indiana 47150 |
| Medical Center Vincennes | Vincennes, Indiana 47591 |
| Southbay Oncology / Hematology Medical Group | Campbell, California 95008 |
| Center for Cancer and Blood Disorders at Suburban Hospital | Bethesda, Maryland 20817 |
| Virginia Oncology Care, PC | Richlands, Virginia 24641 |
| Compassionate Cancer Care Medical Group Incorporated - Fountain Valley | Fountain Valley, California 92708 |
| Signal Point Hematology Oncology Incorporated | Middletown, Ohio 45042 |
| Kansas City Cancer Centers - South | Kansas City, Missouri 64131 |
| Pottsville Cancer Clinic | Pottsville, Pennsylvania 17901 |
| Columbus Clinic, PC | Columbus, Georgia 31901 |
| Anniston Oncology, PC | Anniston, Alabama 36207 |
| Palo Verde Hematology Oncology - Glendale | Glendale, Arizona 85304 |
| Compassionate Cancer Care Medical Group Incorporated - Corona | Corona, California 92882 |
| Advanced Research Management Services, Incorporated | Los Angeles, California 90057 |
| Medical Oncology Care Associates - Orange | Orange, California 92868 |
| Pasco Pinellas Cancer Center - New Port Richey | New Port Richey, Florida 34689 |
| Innovative Medical Research of South Florida, Incorporated | North Miami Beach, Florida 33179-4709 |
| Clintell, Incorporated | Skokie, Illinois 60077 |
| Investigative Clinical Research, LLC | Indianapolis, Indiana 46254 |
| Family Medicine of Vincennes Clinical Trial Center | Vincennes, Indiana 47591 |
| Kentucky Cancer Clinic - Hazard | Hazard, Kentucky 41701 |
| Hematology-Medical Oncology Associates at Central Maine Comprehensive Cancer Center | Lewiston, Maine 04240 |
| Center for Clinical Research at Washington County Hospital | Hagerstown, Maryland 21740 |
| Star Hematology & Oncology | Phillipsburg, New Jersey 08865 |
| Hudson Valley Hematology-Oncology Associates - Poughkeepsie | Poughkeepsie, New York 12601 |
| Comprehensive Cancer Center at Pardee Hospital | Hendersonville, North Carolina 28791 |
| Boice Willis Clinic, PA | Rocky Mount, North Carolina 27804 |
| Eastern North Carolina Medical Group, PLLC | Rocky Mount, North Carolina 27804 |
| Gabrail Cancer Center - Dover Office | Dover, Ohio 44622 |
| Cancer Treatment Centers of America at Southwestern Regional Medical Center | Tulsa, Oklahoma 74133-4564 |
| Charleston Hematology Oncology Associates, PA | Charleston, South Carolina 29403 |
| Julie and Ben Rogers Cancer Institute at Memorial Hermann Baptist Beaumont Hospital | Beaumont, Texas 77701 |
| Texas Cancer Clinic | San Antonio, Texas 78240 |
| Cancer Outreach Associates - Abingdon | Abingdon, Virginia 24211 |
| Western Washington Oncology, Incorporated, PS at Western Washington Cancer Center | Lacey, Washington 98503 |
