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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00343460
First Posted: June 23, 2006
Last Update Posted: February 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Heron Therapeutics
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
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:


Further study details as provided by Heron Therapeutics:

Primary Outcome Measures:
  • Proportion of Patients With Complete Response (CR) During Acute Phase (0-24 Hours) After Administration of Chemotherapy Course 1 [ Time Frame: 0-24 Hours ]
    Complete Response is defined as no emetic episodes and no use of rescue medications

  • Proportion of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1 [ Time Frame: 24-120 Hours ]
    Complete Response is defined as no emetic episodes and no use of rescue medications


Secondary Outcome Measures:
  • Proportion of Patients With Complete Control During the Acute Phase (0-24 Hours), Delayed-onset Phase (24-120 Hours), and During Chemotherapy Course 1 [ Time Frame: 0-120 Hours ]
    Complete control is defined as complete response with no more than mild nausea.

  • Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 1 [ Time Frame: 0-120 Hours ]

    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.


  • Number of Emetic Episodes [ Time Frame: Days 1-5 ]
    Number of Emetic Episodes - days 1-5

  • Time to First Treatment Failure [ Time Frame: 0-120 Hours ]
    Proportions of subjects event free at 24, 48, 72, 96, and 120 hours after chemotherapy administration

  • First and Overall Use of Rescue Medication [ Time Frame: 0-120 Hours ]
  • Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours) [ Time Frame: 0-120 Hours ]
    Maximum severity of nausea, days 1-5

  • Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses [ Time Frame: 0-120 Hours ]

    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


  • Quality of Life and the Impact of Nausea and Vomiting on Day 5 [ Time Frame: 5 days ]
    Functional Living Index

  • Patient's Global Satisfaction With Antiemetic Therapy During Acute Phase and Chemotherapy Course 1 [ Time Frame: 0- 24 Hours ]
    Subject who were very satisfied on Day 1


Enrollment: 1428
Study Start Date: June 2006
Study Completion Date: February 2009
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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00343460


  Show 52 Study Locations
Sponsors and Collaborators
Heron Therapeutics
Investigators
Study Chair: John Barr, PhD Heron Therapeutics
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Heron Therapeutics
ClinicalTrials.gov Identifier: NCT00343460     History of Changes
Other Study ID Numbers: C2006-01
APPA-C2006-01
First Submitted: June 22, 2006
First Posted: June 23, 2006
Results First Submitted: September 9, 2016
Results First Posted: December 28, 2016
Last Update Posted: February 23, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Heron Therapeutics:
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
BB 1101
Palonosetron
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
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