Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT01086605
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 46
• Locations: 230
• Arms: 2
• Actual Duration (Months): 54.5
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as pixantrone dimaleate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pixantrone dimaleate in different ways may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well pixantrone dimaleate works in treating patients with HER2-negative metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: pixantrone dimaleate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To assess the proportion of confirmed tumor responses at each dose level of pixantrone

Secondary

• To describe the distribution of progression-free survival (PFS) times of patients receiving pixantrone

• To assess the 6-month PFS rate in patients receiving each dose level of pixantrone

• To describe the overall survival distribution of patients receiving pixantrone

• To assess the adverse event profile of pixantrone in the treatment of patients with metastatic breast cancer.

• To evaluate the quality of life and patient-reported symptoms of patients receiving the study regimen

OUTLINE: This is a multicenter study. Patients are randomized according to prior doxorubicin treatment ( yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood sample collection at baseline and periodically during study for circulating tumor cells analysis by CellSearch System and mRNA isolation assays.

Patients complete quality-of-life questionnaires using the Linear Analogue Self Assessment (LASA6) and the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline and periodically during study.

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study of Two Doses of Pixantrone in Patients With Metastatic Breast Cancer
• Actual Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Nov 15, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: pixantrone dimaleate; Given IV
Experimental: Arm II Patients receive pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: pixantrone dimaleate; Given IV

Outcome Measures

Primary Outcome Measures

1. Proportion of Confirmed Tumor Responses (Complete or Partial Response) [Up to 5 years]

   The proportion of confirmed responses will be estimated by the number of women who achieve a CR or PR on two consecutive evaluations at least 6-8 weeks apart depending on the dose level. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients at each dose level. Confidence intervals for the true success proportion at each dose level will be calculated according to the approach of Duffy and Santner. Response will be evaluated in this study using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1); Complete Response (CR): Disappearance of all non-nodal target lesions, each target lymph node must have reduction in short axis to <1.0 cm. and normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axis of the target lymph nodes taking as reference the Baseline Sum of Diameters.

Secondary Outcome Measures

1. Time to Disease Progression [Up to 5 years]

   Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression one day post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier at each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).

2. 6-month Progression-free Survival Rate [At 6 months]

   The 6-month progression free survival (6-mo PFS) rate is the proportion of efficacy-evaluable patients progression-free 6 months from registration. The 6-mo PFS rate is defined as the total number of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of efficacy-evaluable patients enrolled on study. Patients who died without documentation of progression will be considered to have progressed on the date of their death. The true 6-mo PFS rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration at each dose level. Binomial confidence intervals for 6-mo PFS rate will be constructed for each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).

3. Overall Survival Time [Up to 5 years]

   Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier at each dose level.

4. Duration of Response [Up to 5 years]

   Duration of response is defined for all evaluable patients with measurable disease who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented at each dose level. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier at each dose level.

5. Toxicity [Up to 1 year after treatment]

   For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Registration and Randomization - Inclusion Criteria

1. Women or men

2. ≥18 years of age

3. Histologically or cytologically confirmed adenocarcinoma of the breast and clinical evidence of metastatic breast cancer.

4. Pre-treatment requirements:

4.1. Must have been previously treated in neoadjuvant, adjuvant or metastatic setting with anthracycline and/or taxane.

4.2. Must have received 2-3 prior chemotherapy treatment regimens NOTE: If NO prior (neo)adjuvant chemotherapy, patient must have received a minimum of 2 prior chemotherapy regimens in the metastatic setting.

4.2.1 NOTE: If prior (neo)adjuvant chemotherapy HAS been given, patient must have received at least 1 prior chemotherapy regimen in the metastatic setting.

4.3. Prior hormonal therapy allowed in the neo-adjuvant, adjuvant, or metastatic setting.

Unlimited prior hormonal therapy is allowed.

1. Patients must have measurable disease as defined in the protocol.

2. Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.

3. The following laboratory values obtained ≤15 days prior to registration.

7.1 Hemoglobin ≥10.0g/dL

7.2 ANC ≥1500/mm^3

7.3 Platelet count ≥100,000/mL

7.4 Total bilirubin ≤1.5 x ULN)

7.5 SGOT (AST) and SGPT (ALT) ≤5 x ULN

7.6 Serum creatinine ≤1.5 x ULN

1. LVEF ≥50% and EKG within institutional normal limits completed ≤22 days prior to registration.

2. ECOG Performance Status (PS) of 0, 1 or 2.

3. Life expectancy >3 months

4. Ability to complete questionnaire(s) by themselves or with assistance.

5. Patient has provided written informed consent

6. Willingness to return to NCCTG enrolling institution for follow-up.

Registration and Randomization - Exclusion Criteria

1. Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.

1.1 Pregnant women

1.2 Nursing women

1.3 Men or women of childbearing potential who are unwilling to employ adequate contraception (as determined by the treating physician)

1. Stage III or IV invasive cancer (other than breast cancer) in ≤3 years prior to registration (with the exception of non-melanoma skin cancer).

2. HER2 positive breast cancer (3+ by IHC or FISH amplified) breast cancer by ASCO/CAP guidelines

3. Has already received lifetime cumulative treatment with doxorubicin equivalent to >400 mg/m2.

4. 3 prior chemotherapy regimens for breast cancer.

5.1 NOTE: This number includes (neo)adjuvant chemotherapy, if given. If (neo)adjuvant chemotherapy HAS been given it counts as one (1) regimen.

1. Major surgery, chemotherapy, or immunologic therapy ≤3 weeks prior to registration.

6.1 NOTE: If patient has received prior treatment with bevacizumab, treatment on this trial should not begin until ≥4 weeks after the last dose of bevacizumab.

1. Radiotherapy ≤4 weeks prior to registration, except if to a non-target lesion only.

7.1 Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.

7.2 If patient receives single dose radiation for palliation or radiation to non-target lesion, they may immediately proceed to registration without waiting.

7.3 Acute adverse events from radiation must have resolved to ≤Grade 1 (according to current version of NCI CTCAE).

1. Evidence of active brain metastasis including leptomeningeal involvement.

8.1 CNS metastasis controlled by prior surgery and/or radiotherapy is allowed. To be considered controlled, there must be at least 2 months of no symptoms or evidence of progression prior to study entry and corticosteroid therapy given to control brain edema must have been discontinued.

1. Uncontrolled hypertension (blood pressure [BP] >160/90mmHg on ≥2 occasions at least 5 minutes apart). (Patients who have recently started or adjusted anti-hypertensive medications are eligible providing that BP is <140/90mmHg on any new regimen for ≥3 different observations in ≥14 days.).

2. Clinically significant cardiovascular or cerebrovascular disease, including any history of the following at any time prior to registration:

10.1 Myocardial infarction

10.2 Unstable angina pectoris

10.3 New York Heart Association (NYHA) Class II or greater congestive heart failure

10.4. Uncontrolled or clinically significant cardiac arrhythmia (patients with controlled atrial fibrillation are eligible)

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.

2. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

3. History of allergy or hypersensitivity to drug product excipients or agents chemically similar to pixantrone.

4. Currently receiving treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered.

14.1 Patient may not enroll in such clinical trials while participating in this study.

Exception may be granted for trials related to symptom management (Cancer Control) which do not employ hormonal treatments or treatments that may block the path of the targeted agents used in this trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
2	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
3	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
4	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii	United States	96701
5	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
6	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii	United States	96813
7	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii	United States	96813
8	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii	United States	96813
9	Hawaii Medical Center - East	Honolulu	Hawaii	United States	96817
10	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii	United States	96817
11	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
12	Kauai Medical Clinic	Lihue	Hawaii	United States	96766
13	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
14	Pacific Cancer Institute - Maui	Wailuku	Hawaii	United States	96793
15	Illinois CancerCare - Bloomington	Bloomington	Illinois	United States	61701
16	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
17	Graham Hospital	Canton	Illinois	United States	61520
18	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
19	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
20	Memorial Hospital	Carthage	Illinois	United States	62321
21	Eureka Community Hospital	Eureka	Illinois	United States	61530
22	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
23	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
24	Illinois CancerCare - Galesburg	Galesburg	Illinois	United States	61401
25	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
26	Mason District Hospital	Havana	Illinois	United States	62644
27	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
28	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
29	McDonough District Hospital	Macomb	Illinois	United States	61455
30	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
31	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
32	Community Cancer Center	Normal	Illinois	United States	61761
33	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
34	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
35	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
36	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
37	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
38	Proctor Hospital	Peoria	Illinois	United States	61614
39	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
40	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
41	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
42	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
43	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
44	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
45	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
46	Perry Memorial Hospital	Princeton	Illinois	United States	61356
47	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
48	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
49	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
50	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
51	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
52	Elkhart General Hospital	Elkhart	Indiana	United States	46515
53	Howard Community Hospital	Kokomo	Indiana	United States	46904
54	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
55	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
56	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
57	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
58	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
59	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
60	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
61	South Bend Clinic	South Bend	Indiana	United States	46617
62	Michiana Hematology Oncology PC - La Porte	Westville	Indiana	United States	46391
63	McFarland Clinic, PC	Ames	Iowa	United States	50010
64	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
65	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
66	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
67	Mercy Cancer Center - West Lakes	Clive	Iowa	United States	50325
68	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
69	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
70	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
71	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
72	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
73	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
74	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
75	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
76	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
77	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
78	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
79	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
80	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
81	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
82	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
83	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
84	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
85	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
86	Hurley Medical Center	Flint	Michigan	United States	48503
87	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
88	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
89	Foote Memorial Hospital	Jackson	Michigan	United States	49201
90	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
91	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
92	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
93	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
94	Michiana Hematology Oncology PC - Niles	Niles	Michigan	United States	49120
95	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
96	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
97	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
98	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
99	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
100	St. John Macomb Hospital	Warren	Michigan	United States	48093
101	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
102	St. Joseph's Medical Center	Brainerd	Minnesota	United States	56401
103	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
104	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
105	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
106	CCOP - Duluth	Duluth	Minnesota	United States	55805
107	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
108	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
109	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
110	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
111	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
112	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
113	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
114	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
115	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
116	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
117	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
118	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
119	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
120	United Hospital	Saint Paul	Minnesota	United States	55102
121	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
122	Lakeview Hospital	Stillwater	Minnesota	United States	55082
123	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
124	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
125	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
126	Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
127	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
128	Comprehensive Cancer Care, PC	Saint Louis	Missouri	United States	63141
129	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
130	St. John's Regional Health Center	Springfield	Missouri	United States	65804
131	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
132	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
133	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
134	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
135	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
136	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
137	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
138	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
139	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
140	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
141	Northern Montana Hospital	Havre	Montana	United States	59501
142	St. Peter's Hospital	Helena	Montana	United States	59601
143	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
144	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
145	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
146	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
147	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
148	Lovelace Medical Center - Downtown	Albuquerque	New Mexico	United States	87102
149	Hematology Oncology Associates, PC	Albuquerque	New Mexico	United States	87106
150	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
151	University of New Mexico Cancer Center - South	Las Cruces	New Mexico	United States	88011
152	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
153	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
154	MeritCare Broadway	Fargo	North Dakota	United States	58122
155	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
156	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
157	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
158	North Coast Cancer Care - Clyde	Clyde	Ohio	United States	43410
159	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
160	CCOP - Columbus	Columbus	Ohio	United States	43215
161	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
162	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
163	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
164	Grandview Hospital	Dayton	Ohio	United States	45405
165	Good Samaritan Hospital	Dayton	Ohio	United States	45406
166	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
167	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
168	CCOP - Dayton	Dayton	Ohio	United States	45420
169	Grady Memorial Hospital	Delaware	Ohio	United States	43015
170	Community Cancer Center	Elyria	Ohio	United States	44035
171	Hematology Oncology Center	Elyria	Ohio	United States	44035
172	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
173	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
174	Wayne Hospital	Greenville	Ohio	United States	45331
175	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
176	Fairfield Medical Center	Lancaster	Ohio	United States	43130
177	Lima Memorial Hospital	Lima	Ohio	United States	45804
178	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
179	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
180	St. Luke's Hospital	Maumee	Ohio	United States	43537
181	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
182	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
183	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
184	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
185	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
186	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
187	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
188	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
189	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
190	Toledo Hospital	Toledo	Ohio	United States	43606
191	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
192	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
193	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
194	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
195	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
196	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
197	Fulton County Health Center	Wauseon	Ohio	United States	43567
198	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
199	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
200	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
201	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
202	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
203	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
204	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
205	Willamette Falls Hospital	Oregon City	Oregon	United States	97045
206	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
207	Adventist Medical Center	Portland	Oregon	United States	97216
208	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
209	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
210	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania	United States	18840
211	AnMed Cancer Center	Anderson	South Carolina	United States	29621
212	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
213	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
214	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
215	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
216	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
217	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
218	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
219	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
220	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
221	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
222	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
223	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
224	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
225	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
226	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
227	St. Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
228	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
229	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
230	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Alvaro Moreno-Asptia, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT01086605
• Other Study ID Numbers: N1031; NCCTG-N1031; CDR0000667253; NCI-2011-02021; U10CA180821; U10CA025224
• First Posted: Mar 15, 2010
• Last Update Posted: May 8, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Alliance for Clinical Trials in Oncology: HER2-negative breast cancer; male breast cancer; recurrent breast cancer; stage IV breast cancer; stage IIIC breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Pixantrone

Study Results

Participant Flow

Arm/Group Title	Arm I/Group A (Pixantrone IV Day 1)	Arm II/Group B (Pixantrone IV Days 1, 8, and 15)
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	24	22
COMPLETED	24	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I/Group A (Pixantrone IV Day 1)	Arm II/Group B (Pixantrone IV Days 1, 8, and 15)	Total
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	24	22	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56.5	52.5	55.5
Sex: Female, Male (Count of Participants)
Female	23 95.8%	22 100%	45 97.8%
Male	1 4.2%	0 0%	1 2.2%
Region of Enrollment (participants) [Number]
United States	24 100%	22 100%	46 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Confirmed Tumor Responses (Complete or Partial Response)
Description	The proportion of confirmed responses will be estimated by the number of women who achieve a CR or PR on two consecutive evaluations at least 6-8 weeks apart depending on the dose level. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients at each dose level. Confidence intervals for the true success proportion at each dose level will be calculated according to the approach of Duffy and Santner. Response will be evaluated in this study using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1); Complete Response (CR): Disappearance of all non-nodal target lesions, each target lymph node must have reduction in short axis to <1.0 cm. and normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axis of the target lymph nodes taking as reference the Baseline Sum of Diameters.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I/Group A (Pixantrone IV Day 1)	Arm II/Group B (Pixantrone IV Days 1, 8, and 15)
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	24	22
Number (95% Confidence Interval) [proportion]	0.08	0.05

2. Secondary Outcome

Title	Time to Disease Progression
Description	Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression one day post-registration. The distribution of time to progression will be estimated using the method of Kaplan-Meier at each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I/Group A (Pixantrone IV Day 1)	Arm II/Group B (Pixantrone IV Days 1, 8, and 15)
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	24	22
Median (95% Confidence Interval) [months]	2.8	2.5

3. Secondary Outcome

Title	6-month Progression-free Survival Rate
Description	The 6-month progression free survival (6-mo PFS) rate is the proportion of efficacy-evaluable patients progression-free 6 months from registration. The 6-mo PFS rate is defined as the total number of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration divided by the total number of efficacy-evaluable patients enrolled on study. Patients who died without documentation of progression will be considered to have progressed on the date of their death. The true 6-mo PFS rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression 6 months from registration at each dose level. Binomial confidence intervals for 6-mo PFS rate will be constructed for each dose level. Progression is defined using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1).
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I/Group A (Pixantrone IV Day 1)	Arm II/Group B (Pixantrone IV Days 1, 8, and 15)
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	24	22
Number (95% Confidence Interval) [proportion]	0.375	0.265

4. Secondary Outcome

Title	Overall Survival Time
Description	Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier at each dose level.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I/Group A (Pixantrone IV Day 1)	Arm II/Group B (Pixantrone IV Days 1, 8, and 15)
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	24	22
Median (95% Confidence Interval) [months]	16.8	9.6

5. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined for all evaluable patients with measurable disease who have achieved a confirmed response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented at each dose level. If a patient dies subsequent to the confirmed response without a documentation of disease progression, the patient will be considered to have had disease progression at the time of their death. In the case of a patient failing to return for evaluations before a documentation of disease progression, the patient will be censored for progression on the date of last evaluation. The distribution of duration of response will be estimated using the method of Kaplan-Meier at each dose level.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I/Group A + Arm II/Group B
Arm/Group Description	Arm I/Group A: Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Arm II/Group B: Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	46
Mean (Full Range) [months]	5.8

6. Secondary Outcome

Title	Toxicity
Description	For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below.
Time Frame	Up to 1 year after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I/Group A (Pixantrone IV Day 1)	Arm II/Group B (Pixantrone IV Days 1, 8, and 15)
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Measure Participants	24	21
Count of Participants [Participants]	16 66.7%	19 86.4%

Adverse Events

Time Frame	Adverse events are assessed within 15 days prior to registration and during the Active Monitoring Phase: less than or equal to 3 days prior to each subsequent cycle of treatment, at end of treatment, and during observation after end of treatment (every 3 months for 1 year).
Adverse Event Reporting Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported.
Arm/Group Title	Arm I/Group A		Arm II/Group B
Arm/Group Description	Patients receive 180 mg/m^2 pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.		Patients receive 85 mg/m^2 pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm I/Group A		Arm II/Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I/Group A		Arm II/Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/24 (12.5%)		9/22 (40.9%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	0/24 (0%)	0	1/22 (4.5%)	1
General disorders
Death NOS	0/24 (0%)	0	1/22 (4.5%)	1
Edema limbs	0/24 (0%)	0	1/22 (4.5%)	1
Fatigue	0/24 (0%)	0	1/22 (4.5%)	1
Hepatobiliary disorders
Hepatic failure	1/24 (4.2%)	1	0/22 (0%)	0
Investigations
Alanine aminotransferase increased	1/24 (4.2%)	1	0/22 (0%)	0
Aspartate aminotransferase increased	1/24 (4.2%)	1	1/22 (4.5%)	1
Blood bilirubin increased	0/24 (0%)	0	1/22 (4.5%)	1
Ejection fraction decreased	1/24 (4.2%)	1	1/22 (4.5%)	1
Lymphocyte count decreased	0/24 (0%)	0	1/22 (4.5%)	1
Neutrophil count decreased	2/24 (8.3%)	2	2/22 (9.1%)	3
White blood cell decreased	0/24 (0%)	0	2/22 (9.1%)	2
Metabolism and nutrition disorders
Hyponatremia	0/24 (0%)	0	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	0/24 (0%)	0	1/22 (4.5%)	1
Nervous system disorders
Peripheral sensory neuropathy	0/24 (0%)	0	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/24 (0%)	0	1/22 (4.5%)	1
Pleural effusion	0/24 (0%)	0	2/22 (9.1%)	2
Pneumonitis	0/24 (0%)	0	1/22 (4.5%)	1
Vascular disorders
Thromboembolic event	0/24 (0%)	0	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Arm I/Group A		Arm II/Group B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/24 (95.8%)		22/22 (100%)
Blood and lymphatic system disorders
Anemia	18/24 (75%)	62	18/22 (81.8%)	43
Blood and lymphatic system disorders - Other, specify	0/24 (0%)	0	1/22 (4.5%)	1
Cardiac disorders
Sinus tachycardia	0/24 (0%)	0	1/22 (4.5%)	1
Ear and labyrinth disorders
Ear pain	0/24 (0%)	0	1/22 (4.5%)	1
Hearing impaired	0/24 (0%)	0	1/22 (4.5%)	1
Eye disorders
Watering eyes	0/24 (0%)	0	2/22 (9.1%)	7
Gastrointestinal disorders
Abdominal pain	1/24 (4.2%)	1	0/22 (0%)	0
Constipation	4/24 (16.7%)	7	3/22 (13.6%)	4
Diarrhea	10/24 (41.7%)	17	6/22 (27.3%)	7
Hemorrhoids	1/24 (4.2%)	1	0/22 (0%)	0
Mucositis oral	8/24 (33.3%)	17	1/22 (4.5%)	1
Nausea	16/24 (66.7%)	54	16/22 (72.7%)	25
Oral pain	0/24 (0%)	0	1/22 (4.5%)	1
Periodontal disease	0/24 (0%)	0	1/22 (4.5%)	3
Vomiting	9/24 (37.5%)	12	9/22 (40.9%)	12
General disorders
Chills	0/24 (0%)	0	1/22 (4.5%)	1
Edema limbs	1/24 (4.2%)	1	1/22 (4.5%)	1
Fatigue	21/24 (87.5%)	76	20/22 (90.9%)	49
Fever	0/24 (0%)	0	2/22 (9.1%)	2
Flu like symptoms	1/24 (4.2%)	1	0/22 (0%)	0
General disorders and administration site conditions - Other, specify	0/24 (0%)	0	1/22 (4.5%)	4
Malaise	0/24 (0%)	0	1/22 (4.5%)	1
Pain	0/24 (0%)	0	2/22 (9.1%)	2
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify	1/24 (4.2%)	1	0/22 (0%)	0
Immune system disorders
Allergic reaction	1/24 (4.2%)	1	0/22 (0%)	0
Infections and infestations
Bronchial infection	1/24 (4.2%)	1	0/22 (0%)	0
Lung infection	1/24 (4.2%)	1	0/22 (0%)	0
Upper respiratory infection	0/24 (0%)	0	1/22 (4.5%)	1
Urinary tract infection	0/24 (0%)	0	1/22 (4.5%)	1
Investigations
Activated partial thromboplastin time prolonged	1/24 (4.2%)	1	0/22 (0%)	0
Alanine aminotransferase increased	4/24 (16.7%)	6	6/22 (27.3%)	8
Alkaline phosphatase increased	1/24 (4.2%)	1	5/22 (22.7%)	5
Aspartate aminotransferase increased	5/24 (20.8%)	10	8/22 (36.4%)	14
Blood bilirubin increased	2/24 (8.3%)	2	4/22 (18.2%)	4
Creatinine increased	2/24 (8.3%)	9	2/22 (9.1%)	3
Ejection fraction decreased	3/24 (12.5%)	3	1/22 (4.5%)	3
Lymphocyte count decreased	2/24 (8.3%)	5	4/22 (18.2%)	5
Neutrophil count decreased	20/24 (83.3%)	40	21/22 (95.5%)	54
Platelet count decreased	5/24 (20.8%)	10	8/22 (36.4%)	10
Weight loss	0/24 (0%)	0	2/22 (9.1%)	5
White blood cell decreased	8/24 (33.3%)	18	7/22 (31.8%)	16
Metabolism and nutrition disorders
Anorexia	2/24 (8.3%)	3	3/22 (13.6%)	10
Hypercalcemia	0/24 (0%)	0	1/22 (4.5%)	2
Hyperglycemia	1/24 (4.2%)	2	2/22 (9.1%)	3
Hypoalbuminemia	0/24 (0%)	0	4/22 (18.2%)	8
Hypocalcemia	0/24 (0%)	0	2/22 (9.1%)	2
Hypokalemia	0/24 (0%)	0	2/22 (9.1%)	2
Hypomagnesemia	1/24 (4.2%)	1	2/22 (9.1%)	2
Hyponatremia	3/24 (12.5%)	4	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/24 (4.2%)	5	1/22 (4.5%)	1
Back pain	1/24 (4.2%)	1	2/22 (9.1%)	7
Bone pain	0/24 (0%)	0	1/22 (4.5%)	1
Buttock pain	1/24 (4.2%)	1	0/22 (0%)	0
Chest wall pain	1/24 (4.2%)	1	2/22 (9.1%)	3
Flank pain	1/24 (4.2%)	1	0/22 (0%)	0
Neck pain	0/24 (0%)	0	1/22 (4.5%)	1
Pain in extremity	0/24 (0%)	0	1/22 (4.5%)	1
Nervous system disorders
Dizziness	1/24 (4.2%)	1	0/22 (0%)	0
Headache	0/24 (0%)	0	1/22 (4.5%)	5
Paresthesia	1/24 (4.2%)	1	0/22 (0%)	0
Peripheral sensory neuropathy	2/24 (8.3%)	3	5/22 (22.7%)	10
Syncope	1/24 (4.2%)	1	0/22 (0%)	0
Psychiatric disorders
Anxiety	0/24 (0%)	0	1/22 (4.5%)	6
Renal and urinary disorders
Urine discoloration	2/24 (8.3%)	2	2/22 (9.1%)	3
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/24 (4.2%)	1	0/22 (0%)	0
Cough	2/24 (8.3%)	3	0/22 (0%)	0
Dyspnea	2/24 (8.3%)	3	1/22 (4.5%)	1
Hoarseness	0/24 (0%)	0	1/22 (4.5%)	2
Skin and subcutaneous tissue disorders
Alopecia	18/24 (75%)	69	16/22 (72.7%)	41
Dry skin	1/24 (4.2%)	1	0/22 (0%)	0
Nail discoloration	0/24 (0%)	0	1/22 (4.5%)	1
Pain of skin	1/24 (4.2%)	1	0/22 (0%)	0
Pruritus	1/24 (4.2%)	1	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders - Other, specify	12/24 (50%)	30	8/22 (36.4%)	25
Skin hyperpigmentation	1/24 (4.2%)	1	0/22 (0%)	0
Vascular disorders
Hot flashes	1/24 (4.2%)	1	0/22 (0%)	0
Hypertension	1/24 (4.2%)	1	1/22 (4.5%)	1
Hypotension	1/24 (4.2%)	1	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.