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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Nausea and Vomiting
• Intervention / Treatment: Drug: Palonosetron Hydrochloride; Drug: dexamethasone; Other: placebo; Drug: APF530

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.

• Study Type: Interventional
• Enrollment (Actual): 1428
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Anniston Oncology, PC
  • Arizona
    • Glendale, Arizona, United States, 85304
      • Palo Verde Hematology Oncology - Glendale
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center, Incorporated
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Incorporated
    • Campbell, California, United States, 95008
      • Southbay Oncology / Hematology Medical Group
    • Corona, California, United States, 92882
      • Compassionate Cancer Care Medical Group Incorporated - Corona
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care Medical Group Incorporated - Fountain Valley
    • Los Angeles, California, United States, 90057
      • Kenmar Research Institute
    • Los Angeles, California, United States, 90057
      • Advanced Research Management Services, Incorporated
    • Orange, California, United States, 92868
      • Medical Oncology Care Associates - Orange
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
  • District of Columbia
    • Washington, District of Columbia, United States, 20017
      • Providence Hospital
  • Florida
    • New Port Richey, Florida, United States, 34689
      • Pasco Pinellas Cancer Center - New Port Richey
    • North Miami Beach, Florida, United States, 33179-4709
      • Innovative Medical Research of South Florida, Incorporated
  • Georgia
    • Columbus, Georgia, United States, 31901
      • Columbus Clinic, PC
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Clintell, Incorporated
  • Indiana
    • Indianapolis, Indiana, United States, 46254
      • Investigative Clinical Research, LLC
    • New Albany, Indiana, United States, 47150
      • Cancer Center of Indiana
    • Vincennes, Indiana, United States, 47591
      • Family Medicine of Vincennes Clinical Trial Center
    • Vincennes, Indiana, United States, 47591
      • Medical Center Vincennes
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Kentucky Cancer Clinic - Hazard
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Cancer Institute, PLLC
  • Maine
    • Lewiston, Maine, United States, 04240
      • Hematology-Medical Oncology Associates at Central Maine Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21202-2165
      • Mercy Medical Center
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders at Suburban Hospital
    • Hagerstown, Maryland, United States, 21740
      • Center for Clinical Research at Washington County Hospital
  • Michigan
    • Petoskey, Michigan, United States, 49770
      • Northern Michigan Hospital
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Cancer Centers - South
  • New Jersey
    • Phillipsburg, New Jersey, United States, 08865
      • Star Hematology & Oncology
  • New York
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center - Buffalo
    • Elmira, New York, United States, 14905
      • Falck Cancer Center at Arnot Ogden Medical Center
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Hematology-Oncology Associates - Poughkeepsie
  • North Carolina
    • Hendersonville, North Carolina, United States, 28791
      • Comprehensive Cancer Center at Pardee Hospital
    • Rocky Mount, North Carolina, United States, 27804
      • Boice Willis Clinic, PA
    • Rocky Mount, North Carolina, United States, 27804
      • Eastern North Carolina Medical Group, PLLC
  • Ohio
    • Akron, Ohio, United States, 44302
      • McDowell Cancer Center at Akron General Medical Center
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center - Canton Office
    • Dover, Ohio, United States, 44622
      • Gabrail Cancer Center - Dover Office
    • Mansfield, Ohio, United States, 44903
      • MedCentral - Mansfield Hospital
    • Middletown, Ohio, United States, 45042
      • Signal Point Hematology Oncology Incorporated
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133-4564
      • Cancer Treatment Centers of America at Southwestern Regional Medical Center
  • Pennsylvania
    • Pottsville, Pennsylvania, United States, 17901
      • Pottsville Cancer Clinic
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Charleston Hematology Oncology Associates, PA
  • Texas
    • Beaumont, Texas, United States, 77701
      • Julie and Ben Rogers Cancer Institute at Memorial Hermann Baptist Beaumont Hospital
    • San Antonio, Texas, United States, 78240
      • Texas Cancer Clinic
  • Virginia
    • Abingdon, Virginia, United States, 24211
      • Cancer Outreach Associates - Abingdon
    • Richlands, Virginia, United States, 24641
      • Virginia Oncology Care, PC
  • Washington
    • Lacey, Washington, United States, 98503
      • Western Washington Oncology, Incorporated, PS at Western Washington Cancer Center
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center at Tacoma General Hospital
  • West Virginia
    • Morgantown, West Virginia, United States, 26506-9300
      • Mary Babb Randolph Cancer Center at West Virginia University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Palonosetron Hydrochloride; Given IV; Drug: dexamethasone; Given IV and orally; 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: dexamethasone; Given IV and orally; Other: placebo; Given subcutanously or IV; Drug: APF530; Given subcutanously
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: dexamethasone; Given IV and orally; Other: placebo; Given subcutanously or IV; Drug: APF530; Given subcutanously

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Complete Control During the Acute Phase (0-24 Hours), Delayed-onset Phase (24-120 Hours), and During Chemotherapy Course 1	Complete control is defined as complete response with no more than mild nausea.	0-120 Hours
Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 1	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.	0-120 Hours
Number of Emetic Episodes	Number of Emetic Episodes - days 1-5	Days 1-5
Time to First Treatment Failure	Proportions of subjects event free at 24, 48, 72, 96, and 120 hours after chemotherapy administration	0-120 Hours
First and Overall Use of Rescue Medication		0-120 Hours
Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours)	Maximum severity of nausea, days 1-5	0-120 Hours
Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses	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	0-120 Hours
Quality of Life and the Impact of Nausea and Vomiting on Day 5	Functional Living Index	5 days
Patient's Global Satisfaction With Antiemetic Therapy During Acute Phase and Chemotherapy Course 1	Subject who were very satisfied on Day 1	0- 24 Hours

Collaborators and Investigators

• Sponsor: Heron Therapeutics
• Investigators: Study Chair: John Barr, PhD, Heron Therapeutics

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: June 22, 2006
• First Submitted That Met QC Criteria: June 22, 2006
• First Posted (Estimate): June 23, 2006

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; nausea and vomiting
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Dexamethasone; Palonosetron
• Other Study ID Numbers: C2006-01; APPA-C2006-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO