Clinical trial NCT00343460: APF530 or Aloxi (Palonosetron Hydrochloride) Combined With Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nausea and Vomiting
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: nausea and vomiting
unspecified adult solid tumor, protocol specific
Lead sponsor: Heron Therapeutics
Sponsor class: INDUSTRY
First posted: 2006-06-23
Enrollment: 1428
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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

Primary outcomes:
measure: Proportion of Patients With Complete Response (CR) During Acute Phase (0-24 Hours) After Administration of Chemotherapy Course 1
timeFrame: 0-24 Hours
measure: Proportion of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1
timeFrame: 24-120 Hours
Secondary outcomes:
measure: Proportion of Patients With Complete Control During the Acute Phase (0-24 Hours), Delayed-onset Phase (24-120 Hours), and During Chemotherapy Course 1
timeFrame: 0-120 Hours
measure: Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 1
timeFrame: 0-120 Hours
measure: Number of Emetic Episodes
timeFrame: Days 1-5
measure: Time to First Treatment Failure
timeFrame: 0-120 Hours
measure: First and Overall Use of Rescue Medication
timeFrame: 0-120 Hours
measure: Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours)
timeFrame: 0-120 Hours
measure: Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses
timeFrame: 0-120 Hours
measure: Quality of Life and the Impact of Nausea and Vomiting on Day 5
timeFrame: 5 days
measure: Patient's Global Satisfaction With Antiemetic Therapy During Acute Phase and Chemotherapy Course 1
timeFrame: 0- 24 Hours
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Anniston Oncology, PC
state: Alabama
city: Glendale
country: United States
facility: Palo Verde Hematology Oncology - Glendale
state: Arizona
city: Tucson
country: United States
facility: Arizona Clinical Research Center, Incorporated
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Incorporated
state: California
city: Campbell
country: United States
facility: Southbay Oncology / Hematology Medical Group
state: California
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group Incorporated - Corona
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group Incorporated - Fountain Valley
state: California
city: Los Angeles
country: United States
facility: Advanced Research Management Services, Incorporated
state: California
city: Los Angeles
country: United States
facility: Kenmar Research Institute
state: California
city: Orange
country: United States
facility: Medical Oncology Care Associates - Orange
state: California
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Washington
country: United States
facility: Providence Hospital
state: District of Columbia
city: New Port Richey
country: United States
facility: Pasco Pinellas Cancer Center - New Port Richey
state: Florida
city: North Miami Beach
country: United States
facility: Innovative Medical Research of South Florida, Incorporated
state: Florida
city: Columbus
country: United States
facility: Columbus Clinic, PC
state: Georgia
city: Skokie
country: United States
facility: Clintell, Incorporated
state: Illinois
city: Indianapolis
country: United States
facility: Investigative Clinical Research, LLC
state: Indiana
city: New Albany
country: United States
facility: Cancer Center of Indiana
state: Indiana
city: Vincennes
country: United States
facility: Family Medicine of Vincennes Clinical Trial Center
state: Indiana
city: Vincennes
country: United States
facility: Medical Center Vincennes
state: Indiana
city: Hazard
country: United States
facility: Kentucky Cancer Clinic - Hazard
state: Kentucky
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute, PLLC
state: Kentucky
city: Lewiston
country: United States
facility: Hematology-Medical Oncology Associates at Central Maine Comprehensive Cancer Center
state: Maine
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders at Suburban Hospital
state: Maryland
city: Hagerstown
country: United States
facility: Center for Clinical Research at Washington County Hospital
state: Maryland
city: Petoskey
country: United States
facility: Northern Michigan Hospital
state: Michigan
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - South
state: Missouri
city: Phillipsburg
country: United States
facility: Star Hematology & Oncology
state: New Jersey
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Elmira
country: United States
facility: Falck Cancer Center at Arnot Ogden Medical Center
state: New York
city: Poughkeepsie
country: United States
facility: Hudson Valley Hematology-Oncology Associates - Poughkeepsie
state: New York
city: Hendersonville
country: United States
facility: Comprehensive Cancer Center at Pardee Hospital
state: North Carolina
city: Rocky Mount
country: United States
facility: Boice Willis Clinic, PA
state: North Carolina
city: Rocky Mount
country: United States
facility: Eastern North Carolina Medical Group, PLLC
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Canton
country: United States
facility: Gabrail Cancer Center - Canton Office
state: Ohio
city: Dover
country: United States
facility: Gabrail Cancer Center - Dover Office
state: Ohio
city: Mansfield
country: United States
facility: MedCentral - Mansfield Hospital
state: Ohio
city: Middletown
country: United States
facility: Signal Point Hematology Oncology Incorporated
state: Ohio
city: Tulsa
country: United States
facility: Cancer Treatment Centers of America at Southwestern Regional Medical Center
state: Oklahoma
city: Pottsville
country: United States
facility: Pottsville Cancer Clinic
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates, PA
state: South Carolina
city: Beaumont
country: United States
facility: Julie and Ben Rogers Cancer Institute at Memorial Hermann Baptist Beaumont Hospital
state: Texas
city: San Antonio
country: United States
facility: Texas Cancer Clinic
state: Texas
city: Abingdon
country: United States
facility: Cancer Outreach Associates - Abingdon
state: Virginia
city: Richlands
country: United States
facility: Virginia Oncology Care, PC
state: Virginia
city: Lacey
country: United States
facility: Western Washington Oncology, Incorporated, PS at Western Washington Cancer Center
state: Washington
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center at Tacoma General Hospital
state: Washington
city: Morgantown
country: United States
facility: Mary Babb Randolph Cancer Center at West Virginia University Hospitals
state: West Virginia
Study officials:
affiliation: Heron Therapeutics
name: John Barr, PhD
role: STUDY_CHAIR
References:
citation: Boccia R, O'Boyle E, Cooper W. Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy. BMC Cancer. 2016 Feb 26;16:166. doi: 10.1186/s12885-016-2186-4.
citation: Raftopoulos H, Boccia R, Cooper W, O'Boyle E, Gralla RJ. Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced nausea/vomiting: analysis by American Society of Clinical Oncology emetogenicity criteria. Future Oncol. 2015 Sep;11(18):2541-51. doi: 10.2217/fon.15.185. Epub 2015 Aug 20.