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

Phase 3
Completed
Conditions
Unspecified Adult Solid Tumor, Protocol Specific
Nausea and Vomiting
Interventions
Registration Number
NCT00343460
Lead Sponsor
Heron Therapeutics
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1428
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm IIAPF530Patients 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 IIplaceboPatients 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 IplaceboPatients 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 IPalonosetron HydrochloridePatients 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 IIIplaceboPatients 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.
Arm IIIAPF530Patients 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.
Arm IdexamethasonePatients 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 IIdexamethasonePatients 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 IIIdexamethasonePatients 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.
Primary Outcome Measures
NameTimeMethod
Proportion of Patients With Complete Response (CR) During Acute Phase (0-24 Hours) After Administration of Chemotherapy Course 10-24 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 124-120 Hours

Complete Response is defined as no emetic episodes and no use of rescue medications

Secondary Outcome Measures
NameTimeMethod
Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 10-120 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.

Proportion of Patients With Complete Control During the Acute Phase (0-24 Hours), Delayed-onset Phase (24-120 Hours), and During Chemotherapy Course 10-120 Hours

Complete control is defined as complete response with no more than mild nausea.

Number of Emetic EpisodesDays 1-5

Number of Emetic Episodes - days 1-5

Time to First Treatment Failure0-120 Hours

Proportions of subjects event free at 24, 48, 72, 96, and 120 hours after chemotherapy administration

First and Overall Use of Rescue Medication0-120 Hours
Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours)0-120 Hours

Maximum severity of nausea, days 1-5

Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses0-120 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 55 days

Functional Living Index

Patient's Global Satisfaction With Antiemetic Therapy During Acute Phase and Chemotherapy Course 10- 24 Hours

Subject who were very satisfied on Day 1

Trial Locations

Locations (52)

Anniston Oncology, PC

🇺🇸

Anniston, Alabama, United States

Palo Verde Hematology Oncology - Glendale

🇺🇸

Glendale, Arizona, United States

Arizona Clinical Research Center, Incorporated

🇺🇸

Tucson, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Pacific Cancer Medical Center, Incorporated

🇺🇸

Anaheim, California, United States

Southbay Oncology / Hematology Medical Group

🇺🇸

Campbell, California, United States

Compassionate Cancer Care Medical Group Incorporated - Corona

🇺🇸

Corona, California, United States

Compassionate Cancer Care Medical Group Incorporated - Fountain Valley

🇺🇸

Fountain Valley, California, United States

Advanced Research Management Services, Incorporated

🇺🇸

Los Angeles, California, United States

Kenmar Research Institute

🇺🇸

Los Angeles, California, United States

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Anniston Oncology, PC
🇺🇸Anniston, Alabama, United States

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