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

• Sponsor: Heron Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00343460
• Collaborator: (none)
• Enrollment: 1,428
• Locations: 52
• Arms: 3
• Duration (Months): 32.1
• Patients Per Site: 27.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Nausea and Vomiting; Unspecified Adult Solid Tumor, Protocol Specific	Drug: APF530; Drug: dexamethasone; Drug: Palonosetron Hydrochloride; Other: placebo	Phase 3

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

• 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 Design

• Study Type: Interventional
• Actual Enrollment: 1428 participants
• 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
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

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: 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

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Complete Response (CR) During Acute Phase (0-24 Hours) After Administration of Chemotherapy Course 1 [0-24 Hours]

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

2. Proportion of Patients With CR During Delayed-onset Phase (24-120 Hours) After Administration of Chemotherapy Course 1 [24-120 Hours]

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

Secondary Outcome Measures

1. Proportion of Patients With Complete Control During the Acute Phase (0-24 Hours), Delayed-onset Phase (24-120 Hours), and During Chemotherapy Course 1 [0-120 Hours]

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

2. Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 1 [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.

3. Number of Emetic Episodes [Days 1-5]

   Number of Emetic Episodes - days 1-5

4. Time to First Treatment Failure [0-120 Hours]

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

5. First and Overall Use of Rescue Medication [0-120 Hours]

6. Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours) [0-120 Hours]

   Maximum severity of nausea, days 1-5

7. Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses [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

8. Quality of Life and the Impact of Nausea and Vomiting on Day 5 [5 days]

   Functional Living Index

9. Patient's Global Satisfaction With Antiemetic Therapy During Acute Phase and Chemotherapy Course 1 [0- 24 Hours]

   Subject who were very satisfied on Day 1

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

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

Sponsors and Collaborators

• Heron Therapeutics

Investigators

• Study Chair: John Barr, PhD, Heron Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Heron Therapeutics
• ClinicalTrials.gov Identifier: NCT00343460
• Other Study ID Numbers: C2006-01; APPA-C2006-01
• First Posted: Jun 23, 2006
• Last Update Posted: Feb 23, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Dexamethasone; Palonosetron

Study Results

Participant Flow

Arm/Group Title	APF530 5 mg	APF530 10 mg	Aloxi 0.25 mg
Arm/Group Description	APF530 5 mg - Safety Population	APF530 10 mg - Safety Population	Aloxi 0.25 mg - Safety Population
Period Title: Cycle 1
STARTED	475	481	472
COMPLETED	453	459	454
NOT COMPLETED	22	22	18
Period Title: Cycle 1
STARTED	584	565	0
COMPLETED	528	515	0
NOT COMPLETED	56	50	0

Baseline Characteristics

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 Highly	Total
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Total of all reporting groups
Overall Participants	214	212	208	229	240	238	1341
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.8 (12.80)	55.1 (12.79)	57.3 (12.36)	57.6 (13.35)	56.8 (13.20)	58.1 (13.74)	56.62 (13.04)
Sex: Female, Male (Count of Participants)
Female	189 88.3%	177 83.5%	177 85.1%	153 66.8%	152 63.3%	158 66.4%	1006 75%
Male	25 11.7%	35 16.5%	31 14.9%	76 33.2%	88 36.7%	80 33.6%	335 25%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	214	212	208	229	240	238
Number [participants]	160 74.8%	163 76.9%	156 75%	178 77.7%	195 81.3%	192 80.7%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	214	212	208	229	240	238
Number [participants]	110 51.4%	125 59%	120 57.7%	148 64.6%	164 68.3%	158 66.4%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	214	212	208	229	240	238
CC during acute Phase	154 72%	152 71.7%	147 70.7%	170 74.2%	183 76.3%	184 77.3%
CC during the delayed-onset phase	100 46.7%	115 54.2%	107 51.4%	138 60.3%	150 62.5%	147 61.8%
CC during the overall risk period	93 43.5%	107 50.5%	99 47.6%	127 55.5%	138 57.5%	136 57.1%

4. Secondary Outcome

Title	Proportion of Patients With Total Response During the Acute Phase, Delayed-onset Phase, and During Chemotherapy Course 1
Description	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.
Time Frame	0-120 Hours

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	214	212	208	229	240	238
TR during acute phase	135 63.1%	121 57.1%	113 54.3%	141 61.6%	146 60.8%	158 66.4%
TR during the delayed-onset phase	76 35.5%	89 42%	73 35.1%	115 50.2%	113 47.1%	122 51.3%
TR during the overall risk period	68 31.8%	79 37.3%	65 31.3%	103 45%	101 42.1%	117 49.2%

5. Secondary Outcome

Title	Number of Emetic Episodes
Description	Number of Emetic Episodes - days 1-5
Time Frame	Days 1-5

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	208	208	205	217	236	222
Mean (Standard Deviation) [Number of Emetic Episodes]	3.4 (8.03)	3.1 (9.35)	2.1 (5.12)	2.3 (6.69)	2.4 (7.87)	2.5 (7.15)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Proportions of subjects event free in Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 - Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	214	211	208	228	238	238
24 Hours	0.738	0.763	0.755	0.781	0.811	0.803
48 Hours	0.636	0.659	0.635	0.706	0.723	0.714
72 Hours	0.533	0.564	0.567	0.649	0.685	0.672
96 Hours	0.485	0.550	0.534	0.618	0.668	0.634
120 Hours	0.485	0.540	0.529	0.600	0.647	0.620

7. Secondary Outcome

Title	First and Overall Use of Rescue Medication
Time Frame	0-120 Hours

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 - Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	214	212	208	229	240	238
Used Rescue Medication, 0-24 hours	42 19.6%	37 17.5%	41 19.7%	35 15.3%	23 9.6%	25 10.5%
Used Rescue Medication, 24-120 hours	83 38.8%	69 32.5%	63 30.3%	60 26.2%	42 17.5%	42 17.6%
Used Rescue Medication, 0-120 hours	89 41.6%	76 35.8%	72 34.6%	71 31%	45 18.8%	49 20.6%

8. Secondary Outcome

Title	Severity of Nausea Daily and During Chemotherapy Course 1 (0-120 Hours)
Description	Maximum severity of nausea, days 1-5
Time Frame	0-120 Hours

Outcome Measure Data

Analysis Population Description

Severity of Nausea - Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 - Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	212	210	204	219	235	232
None	78 36.4%	85 40.1%	66 31.7%	105 45.9%	102 42.5%	121 50.8%
Mild	45 21%	53 25%	68 32.7%	53 23.1%	68 28.3%	53 22.3%
Moderate	59 27.6%	40 18.9%	46 22.1%	48 21%	37 15.4%	39 16.4%
Severe	30 14%	32 15.1%	24 11.5%	13 5.7%	28 11.7%	19 8%

9. Secondary Outcome

Title	Sustainability of Antiemetic Effect of APF530 Over Multiple Chemotherapy Courses
Description	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
Time Frame	0-120 Hours

Outcome Measure Data

Analysis Population Description

Number of subjects in the Modified Intent-to-Treat Population with overall CR (0-120 hrs) in all cycles

Arm/Group Title	Cycles 1, 2, 3 and 4 - Moderately	Cycles 1, 2, 3, and 4 - Moderately	Cycles 1, 2, 3 and 4 - Highly	Cycles 1, 2, 3, and 4 - Highly
Arm/Group Description	APF530 5 mg	APF530 10 mg	APF530 5 mg	APF530 10 mg
Measure Participants	91	92	106	95
Number [participants with overall CR]	34 15.9%	35 16.5%	56 26.9%	52 22.7%

10. Secondary Outcome

Title	Quality of Life and the Impact of Nausea and Vomiting on Day 5
Description	Functional Living Index
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population (All Languages Except Punjabi)

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 - Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	208	210	204	223	228	231
No nausea impact on daily life	112 52.3%	127 59.9%	120 57.7%	142 62%	142 59.2%	159 66.8%
No vomiting impact on daily life	157 73.4%	162 76.4%	160 76.9%	173 75.5%	182 75.8%	191 80.3%

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Cycle 1 - Modified Intent-to-Treat Population

Arm/Group Title	Cycle 1 APF530 5 mg - Moderately	Cycle 1 APF530 10 mg - Moderately	Cycle 1 Aloxi 0.25 mg - Moderately	Cycle 1 APF530 5 mg - Highly	Cycle 1 APF530 10 mg - Highly	Cycle 1 Aloxi 0.25 - Highly
Arm/Group Description	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Moderately	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly	Cycle 1 - Modified Intent-to-Treat Population Emetogenic Status: Highly
Measure Participants	211	212	208	229	240	238
Number [participants]	101 47.2%	113 53.3%	98 47.1%	128 55.9%	128 53.3%	135 56.7%

Adverse Events

Arm/Group Title	Cycle 1 APF530 5 mg		Cycle 1 APF530 10 mg		Cycle 1 Aloxi 0.25 mg		Cycles 2-4 APF530 5 mg		Cycle 2-4 APF530 10 mg
Arm/Group Description	Serious Treatment-Emergent Adverse Events - Cycle 1 - Safety Population		Serious Treatment-Emergent Adverse Events - Cycle 1 - Safety Population		Serious Treatment-Emergent Adverse Events - Cycle 1 - Safety Population		Serious Treatment-Emergent Adverse Events - Cycles 2-4 - Safety Population		Serious Treatment-Emergent Adverse Events - Cycles 2-4 - Safety Population
All Cause Mortality
	Cycle 1 APF530 5 mg		Cycle 1 APF530 10 mg		Cycle 1 Aloxi 0.25 mg		Cycles 2-4 APF530 5 mg		Cycle 2-4 APF530 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cycle 1 APF530 5 mg		Cycle 1 APF530 10 mg		Cycle 1 Aloxi 0.25 mg		Cycles 2-4 APF530 5 mg		Cycle 2-4 APF530 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/464 (9.1%)		36/468 (7.7%)		27/472 (5.7%)		61/528 (11.6%)		73/515 (14.2%)
Blood and lymphatic system disorders
Anaemia	2/464 (0.4%)		0/468 (0%)		2/472 (0.4%)		6/528 (1.1%)		2/515 (0.4%)
Febrile neutropenia	2/464 (0.4%)		7/468 (1.5%)		3/472 (0.6%)		5/528 (0.9%)		8/515 (1.6%)
Leukocytosis	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Leukopenia	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		1/515 (0.2%)
Neutropenia	2/464 (0.4%)		1/468 (0.2%)		2/472 (0.4%)		2/528 (0.4%)		6/515 (1.2%)
Pancytopenia	2/464 (0.4%)		2/468 (0.4%)		1/472 (0.2%)		2/528 (0.4%)		2/515 (0.4%)
Splenomegaly	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Thrombocytopenia	3/464 (0.6%)		1/468 (0.2%)		0/472 (0%)		1/528 (0.2%)		3/515 (0.6%)
Cardiac disorders
Acute coronary syndrome	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Acute myocardial infarction	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Atrial fibrillation	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Cardiac arrest	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Cardiac failure congestive	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		2/515 (0.4%)
Cardio-respiratory arrest	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Myocardial infarction	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Sinus tachycardia	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Sudden Death	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Tachycardia	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Ventricular tachycardia	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Ear and labyrinth disorders
Vertigo	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Endocrine disorders
Diabetes mellitus	1/464 (0.2%)		0/468 (0%)		1/472 (0.2%)		1/528 (0.2%)		0/515 (0%)
Hyperglycaemia	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		2/515 (0.4%)
Gastrointestinal disorders
Abdominal distension	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Abdominal pain	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		1/528 (0.2%)		2/515 (0.4%)
Abdominal pain upper	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Constipation	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Diarrhoea	2/464 (0.4%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		2/515 (0.4%)
Diverticulitis	0/464 (0%)		2/468 (0.4%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Dysphagia	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Erosive oesophagitis	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Faecaloma	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Gastric perforation	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Gastrointestinal haemorrhage	0/464 (0%)		0/468 (0%)		0/472 (0%)		2/528 (0.4%)		2/515 (0.4%)
Hiatus hernia	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Ileus	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Intestinal obstruction	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Nausea	1/464 (0.2%)		3/468 (0.6%)		2/472 (0.4%)		3/528 (0.6%)		1/515 (0.2%)
Oesophageal carcinoma recurrent	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Oesophagitis	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Peptic ulcer haemorrhage	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Rectal haemorrhage	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Small intestinal perforation	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Vomiting	1/464 (0.2%)		4/468 (0.9%)		1/472 (0.2%)		1/528 (0.2%)		3/515 (0.6%)
General disorders
Asthenia	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		1/528 (0.2%)		1/515 (0.2%)
Chest pain	1/464 (0.2%)		1/468 (0.2%)		1/472 (0.2%)		1/528 (0.2%)		2/515 (0.4%)
Death	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Drug hypersensitivity	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		2/515 (0.4%)
Fatigue	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Injection site haemorrhage	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Multi-organ failure	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Oedema peripheral	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Pain	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Pyrexia	1/464 (0.2%)		0/468 (0%)		1/472 (0.2%)		3/528 (0.6%)		1/515 (0.2%)
Hepatobiliary disorders
Cholelithiasis	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Hepatic failure	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Immune system disorders
Anaphylactic reaction	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Infections and infestations
Bacteraemia	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Bronchitis chronic	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Bronchopulmonary aspergillosis	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Catheter related infection	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Catheter site infection	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		2/515 (0.4%)
Cellulitis	1/464 (0.2%)		0/468 (0%)		1/472 (0.2%)		1/528 (0.2%)		1/515 (0.2%)
Clostridium difficile colitis	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Escherichia infection	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Gastroenteritis	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Gastroenteritis viral	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Infection	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Osteomyelitis	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Pneumonia	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		7/528 (1.3%)		4/515 (0.8%)
Respiratory tract infection	0/464 (0%)		1/468 (0.2%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Sepsis	1/464 (0.2%)		1/468 (0.2%)		2/472 (0.4%)		4/528 (0.8%)		1/515 (0.2%)
Septic shock	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		1/515 (0.2%)
Staphylococcal infection	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		1/528 (0.2%)		2/515 (0.4%)
Urinary tract infection	1/464 (0.2%)		1/468 (0.2%)		0/472 (0%)		2/528 (0.4%)		1/515 (0.2%)
Wound infection	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Injury, poisoning and procedural complications
Drug toxicity	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Facial bones fracture	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Femur fracture	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Hip fracture	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Investigations
Prothrombin level abnormal	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Weight decreased	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Metabolism and nutrition disorders
Dehydration	1/464 (0.2%)		2/468 (0.4%)		2/472 (0.4%)		4/528 (0.8%)		6/515 (1.2%)
Hypokalaemia	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Hyponatraemia	1/464 (0.2%)		0/468 (0%)		1/472 (0.2%)		1/528 (0.2%)		0/515 (0%)
Malnutrition	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Musculoskeletal and connective tissue disorders
Costochondritis	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Intervertebral disc protrusion	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Pain in extremity	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		1/528 (0.2%)		0/515 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Malignant neoplasm progression	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		2/515 (0.4%)
Metastases to central nervous system	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Nervous system disorders
Convulsion	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Headache	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		1/515 (0.2%)
Loss of consciousness	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Presyncope	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Somnolence	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Spinal cord compression	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Syncope	2/464 (0.4%)		0/468 (0%)		0/472 (0%)		2/528 (0.4%)		0/515 (0%)
Psychiatric disorders
Anxiety	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Delirium	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Renal and urinary disorders
Bladder cancer	0/464 (0%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Haematuria	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Nephropathy	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Renal failure	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/464 (0%)		0/468 (0%)		0/472 (0%)		2/528 (0.4%)		0/515 (0%)
Dyspnoea	3/464 (0.6%)		2/468 (0.4%)		0/472 (0%)		2/528 (0.4%)		3/515 (0.6%)
Hypoxia	0/464 (0%)		1/468 (0.2%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Pleural effusion	3/464 (0.6%)		0/468 (0%)		0/472 (0%)		4/528 (0.8%)		0/515 (0%)
Pleuritic pain	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Pulmonary embolism	1/464 (0.2%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		6/515 (1.2%)
Respiratory failure	2/464 (0.4%)		3/468 (0.6%)		1/472 (0.2%)		4/528 (0.8%)		1/515 (0.2%)
Throat tightness	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Surgical and medical procedures
Appendicectomy	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Mastectomy	0/464 (0%)		1/468 (0.2%)		0/472 (0%)		0/528 (0%)		1/515 (0.2%)
Tumour excision	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Vascular disorders
Cerebrovascular accident	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		1/528 (0.2%)		0/515 (0%)
Deep vein thrombosis	2/464 (0.4%)		1/468 (0.2%)		0/472 (0%)		4/528 (0.8%)		3/515 (0.6%)
Epistaxis	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		1/515 (0.2%)
Haematoma	0/464 (0%)		0/468 (0%)		1/472 (0.2%)		0/528 (0%)		0/515 (0%)
Hypotension	1/464 (0.2%)		1/468 (0.2%)		0/472 (0%)		3/528 (0.6%)		0/515 (0%)
Orthostatic hypotension	1/464 (0.2%)		0/468 (0%)		0/472 (0%)		0/528 (0%)		0/515 (0%)
Septic phlebitis	0/464 (0%)		0/468 (0%)		0/472 (0%)		1/528 (0.2%)		0/515 (0%)
Other (Not Including Serious) Adverse Events
	Cycle 1 APF530 5 mg		Cycle 1 APF530 10 mg		Cycle 1 Aloxi 0.25 mg		Cycles 2-4 APF530 5 mg		Cycle 2-4 APF530 10 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	335/464 (72.2%)		349/468 (74.6%)		313/472 (66.3%)		422/528 (79.9%)		413/515 (80.2%)
Blood and lymphatic system disorders
Anaemia	46/464 (9.9%)		42/468 (9%)		34/472 (7.2%)		86/528 (16.3%)		87/515 (16.9%)
Neutropenia	39/464 (8.4%)		48/468 (10.3%)		38/472 (8.1%)		46/528 (8.7%)		42/515 (8.2%)
Thrombocytopenia	18/464 (3.9%)		16/468 (3.4%)		13/472 (2.8%)		32/528 (6.1%)		36/515 (7%)
Gastrointestinal disorders
Abdominal pain	21/464 (4.5%)		13/468 (2.8%)		28/472 (5.9%)		15/528 (2.8%)		24/515 (4.7%)
Constipation	61/464 (13.1%)		72/468 (15.4%)		62/472 (13.1%)		78/528 (14.8%)		79/515 (15.3%)
Diarrhoea	47/464 (10.1%)		44/468 (9.4%)		39/472 (8.3%)		51/528 (9.7%)		69/515 (13.4%)
Dyspepsia	16/464 (3.4%)		16/468 (3.4%)		16/472 (3.4%)		32/528 (6.1%)		30/515 (5.8%)
Nausea	55/464 (11.9%)		58/468 (12.4%)		41/472 (8.7%)		66/528 (12.5%)		73/515 (14.2%)
Vomiting	24/464 (5.2%)		18/468 (3.8%)		13/472 (2.8%)		28/528 (5.3%)		25/515 (4.9%)
General disorders
Asthenia	23/464 (5%)		21/468 (4.5%)		30/472 (6.4%)		60/528 (11.4%)		39/515 (7.6%)
Fatigue	62/464 (13.4%)		62/468 (13.2%)		52/472 (11%)		80/528 (15.2%)		94/515 (18.3%)
Injection site bruising	78/464 (16.8%)		93/468 (19.9%)		41/472 (8.7%)		124/528 (23.5%)		153/515 (29.7%)
Injection site erythema	33/464 (7.1%)		51/468 (10.9%)		14/472 (3%)		58/528 (11%)		61/515 (11.8%)
Injection site haemorrhage	20/464 (4.3%)		18/468 (3.8%)		10/472 (2.1%)		35/528 (6.6%)		31/515 (6%)
Injection site nodule	22/464 (4.7%)		50/468 (10.7%)		3/472 (0.6%)		57/528 (10.8%)		90/515 (17.5%)
Injection site pain	16/464 (3.4%)		33/468 (7.1%)		5/472 (1.1%)		34/528 (6.4%)		37/515 (7.2%)
Oedema peripheral	13/464 (2.8%)		7/468 (1.5%)		8/472 (1.7%)		28/528 (5.3%)		31/515 (6%)
Pyrexia	15/464 (3.2%)		15/468 (3.2%)		19/472 (4%)		32/528 (6.1%)		24/515 (4.7%)
Infections and infestations
Upper respiratory tract infection	4/464 (0.9%)		4/468 (0.9%)		9/472 (1.9%)		29/528 (5.5%)		21/515 (4.1%)
Metabolism and nutrition disorders
Decreased appetite	13/464 (2.8%)		17/468 (3.6%)		17/472 (3.6%)		24/528 (4.5%)		32/515 (6.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	14/464 (3%)		11/468 (2.4%)		10/472 (2.1%)		35/528 (6.6%)		29/515 (5.6%)
Pain in extremity	10/464 (2.2%)		10/468 (2.1%)		10/472 (2.1%)		29/528 (5.5%)		21/515 (4.1%)
Nervous system disorders
Dizziness	14/464 (3%)		17/468 (3.6%)		8/472 (1.7%)		21/528 (4%)		29/515 (5.6%)
Headache	31/464 (6.7%)		47/468 (10%)		44/472 (9.3%)		38/528 (7.2%)		44/515 (8.5%)
Insomnia	20/464 (4.3%)		25/468 (5.3%)		11/472 (2.3%)		27/528 (5.1%)		23/515 (4.5%)
Respiratory, thoracic and mediastinal disorders
Cough	11/464 (2.4%)		11/468 (2.4%)		14/472 (3%)		31/528 (5.9%)		34/515 (6.6%)
Dyspnoea	13/464 (2.8%)		12/468 (2.6%)		9/472 (1.9%)		35/528 (6.6%)		19/515 (3.7%)
Skin and subcutaneous tissue disorders
Alopecia	19/464 (4.1%)		31/468 (6.6%)		25/472 (5.3%)		82/528 (15.5%)		69/515 (13.4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A period of 60 working days for presentational material and abstracts and 90 days for manuscripts is permitted for the sponsor's review. The sponsor can request modifications of any manuscript or other materials to be published or presented. The sponsor can also request additional time to obtain additional patent protection or take such other measures to establish and preserve its intellectual property and proprietary rights before publishing information from this trial.