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

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ClinicalTrials.gov Identifier: NCT01086605
Recruitment Status : Completed
First Posted : March 15, 2010
Results First Posted : February 23, 2017
Last Update Posted : May 8, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Breast Cancer
Intervention Drug: pixantrone dimaleate
Enrollment 46
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I/Group A (Pixantrone IV Day 1) Arm II/Group B (Pixantrone IV Days 1, 8, and 15)
Hide 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
Arm/Group Title Arm I/Group A (Pixantrone IV Day 1) Arm II/Group B (Pixantrone IV Days 1, 8, and 15) Total
Hide 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 Number of Baseline Participants 24 22 46
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 24 participants 22 participants 46 participants
56.5
(42 to 79)
52.5
(38 to 75)
55.5
(38 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 22 participants 46 participants
Female
23
  95.8%
22
 100.0%
45
  97.8%
Male
1
   4.2%
0
   0.0%
1
   2.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants 22 participants 46 participants
24 22 46
1.Primary Outcome
Title Proportion of Confirmed Tumor Responses (Complete or Partial Response)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 24 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion
0.08
(0.01 to 0.27)
0.05
(0 to 0.24)
2.Secondary Outcome
Title Time to Disease Progression
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 24 22
Median (95% Confidence Interval)
Unit of Measure: months
2.8
(1.4 to 7.9)
2.5
(1.7 to 4.1)
3.Secondary Outcome
Title 6-month Progression-free Survival Rate
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 24 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion
0.375
(0.224 to 0.629)
0.265
(0.227 to 0.553)
4.Secondary Outcome
Title Overall Survival Time
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 24 22
Median (95% Confidence Interval)
Unit of Measure: months
16.8 [1] 
(9 to NA)
9.6 [1] 
(4.7 to NA)
[1]
The study did not have enough deaths or patients were not followed long enough to get the upper limit of the 95% confidence interval of median overall survival.
5.Secondary Outcome
Title Duration of Response
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I/Group A + Arm II/Group B
Hide 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.

Overall Number of Participants Analyzed 46
Mean (Full Range)
Unit of Measure: months
5.8
(4.6 to 7.2)
6.Secondary Outcome
Title Toxicity
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 24 21
Measure Type: Count of Participants
Unit of Measure: Participants
16
  66.7%
19
  90.5%
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
Hide 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 (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I/Group A Arm II/Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/24 (12.50%)      9/22 (40.91%)    
Blood and lymphatic system disorders     
Disseminated intravascular coagulation  1  0/24 (0.00%)  0 1/22 (4.55%)  1
General disorders     
Death NOS  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Edema limbs  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Fatigue  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Hepatobiliary disorders     
Hepatic failure  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Aspartate aminotransferase increased  1  1/24 (4.17%)  1 1/22 (4.55%)  1
Blood bilirubin increased  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Ejection fraction decreased  1  1/24 (4.17%)  1 1/22 (4.55%)  1
Lymphocyte count decreased  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Neutrophil count decreased  1  2/24 (8.33%)  2 2/22 (9.09%)  3
White blood cell decreased  1  0/24 (0.00%)  0 2/22 (9.09%)  2
Metabolism and nutrition disorders     
Hyponatremia  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Nervous system disorders     
Peripheral sensory neuropathy  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnea  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Pleural effusion  1  0/24 (0.00%)  0 2/22 (9.09%)  2
Pneumonitis  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Vascular disorders     
Thromboembolic event  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I/Group A Arm II/Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/24 (95.83%)      22/22 (100.00%)    
Blood and lymphatic system disorders     
Anemia  1  18/24 (75.00%)  62 18/22 (81.82%)  43
Blood and lymphatic system disorders - Other, specify  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Cardiac disorders     
Sinus tachycardia  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Ear and labyrinth disorders     
Ear pain  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Hearing impaired  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Eye disorders     
Watering eyes  1  0/24 (0.00%)  0 2/22 (9.09%)  7
Gastrointestinal disorders     
Abdominal pain  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Constipation  1  4/24 (16.67%)  7 3/22 (13.64%)  4
Diarrhea  1  10/24 (41.67%)  17 6/22 (27.27%)  7
Hemorrhoids  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Mucositis oral  1  8/24 (33.33%)  17 1/22 (4.55%)  1
Nausea  1  16/24 (66.67%)  54 16/22 (72.73%)  25
Oral pain  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Periodontal disease  1  0/24 (0.00%)  0 1/22 (4.55%)  3
Vomiting  1  9/24 (37.50%)  12 9/22 (40.91%)  12
General disorders     
Chills  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Edema limbs  1  1/24 (4.17%)  1 1/22 (4.55%)  1
Fatigue  1  21/24 (87.50%)  76 20/22 (90.91%)  49
Fever  1  0/24 (0.00%)  0 2/22 (9.09%)  2
Flu like symptoms  1  1/24 (4.17%)  1 0/22 (0.00%)  0
General disorders and administration site conditions - Other, specify  1  0/24 (0.00%)  0 1/22 (4.55%)  4
Malaise  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Pain  1  0/24 (0.00%)  0 2/22 (9.09%)  2
Hepatobiliary disorders     
Hepatobiliary disorders - Other, specify  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Immune system disorders     
Allergic reaction  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Infections and infestations     
Bronchial infection  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Lung infection  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Upper respiratory infection  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Urinary tract infection  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Investigations     
Activated partial thromboplastin time prolonged  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Alanine aminotransferase increased  1  4/24 (16.67%)  6 6/22 (27.27%)  8
Alkaline phosphatase increased  1  1/24 (4.17%)  1 5/22 (22.73%)  5
Aspartate aminotransferase increased  1  5/24 (20.83%)  10 8/22 (36.36%)  14
Blood bilirubin increased  1  2/24 (8.33%)  2 4/22 (18.18%)  4
Creatinine increased  1  2/24 (8.33%)  9 2/22 (9.09%)  3
Ejection fraction decreased  1  3/24 (12.50%)  3 1/22 (4.55%)  3
Lymphocyte count decreased  1  2/24 (8.33%)  5 4/22 (18.18%)  5
Neutrophil count decreased  1  20/24 (83.33%)  40 21/22 (95.45%)  54
Platelet count decreased  1  5/24 (20.83%)  10 8/22 (36.36%)  10
Weight loss  1  0/24 (0.00%)  0 2/22 (9.09%)  5
White blood cell decreased  1  8/24 (33.33%)  18 7/22 (31.82%)  16
Metabolism and nutrition disorders     
Anorexia  1  2/24 (8.33%)  3 3/22 (13.64%)  10
Hypercalcemia  1  0/24 (0.00%)  0 1/22 (4.55%)  2
Hyperglycemia  1  1/24 (4.17%)  2 2/22 (9.09%)  3
Hypoalbuminemia  1  0/24 (0.00%)  0 4/22 (18.18%)  8
Hypocalcemia  1  0/24 (0.00%)  0 2/22 (9.09%)  2
Hypokalemia  1  0/24 (0.00%)  0 2/22 (9.09%)  2
Hypomagnesemia  1  1/24 (4.17%)  1 2/22 (9.09%)  2
Hyponatremia  1  3/24 (12.50%)  4 0/22 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/24 (4.17%)  5 1/22 (4.55%)  1
Back pain  1  1/24 (4.17%)  1 2/22 (9.09%)  7
Bone pain  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Buttock pain  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Chest wall pain  1  1/24 (4.17%)  1 2/22 (9.09%)  3
Flank pain  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Neck pain  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Pain in extremity  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Nervous system disorders     
Dizziness  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Headache  1  0/24 (0.00%)  0 1/22 (4.55%)  5
Paresthesia  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Peripheral sensory neuropathy  1  2/24 (8.33%)  3 5/22 (22.73%)  10
Syncope  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Psychiatric disorders     
Anxiety  1  0/24 (0.00%)  0 1/22 (4.55%)  6
Renal and urinary disorders     
Urine discoloration  1  2/24 (8.33%)  2 2/22 (9.09%)  3
Respiratory, thoracic and mediastinal disorders     
Allergic rhinitis  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Cough  1  2/24 (8.33%)  3 0/22 (0.00%)  0
Dyspnea  1  2/24 (8.33%)  3 1/22 (4.55%)  1
Hoarseness  1  0/24 (0.00%)  0 1/22 (4.55%)  2
Skin and subcutaneous tissue disorders     
Alopecia  1  18/24 (75.00%)  69 16/22 (72.73%)  41
Dry skin  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Nail discoloration  1  0/24 (0.00%)  0 1/22 (4.55%)  1
Pain of skin  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Pruritus  1  1/24 (4.17%)  1 1/22 (4.55%)  1
Skin and subcutaneous tissue disorders - Other, specify  1  12/24 (50.00%)  30 8/22 (36.36%)  25
Skin hyperpigmentation  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Vascular disorders     
Hot flashes  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Hypertension  1  1/24 (4.17%)  1 1/22 (4.55%)  1
Hypotension  1  1/24 (4.17%)  1 0/22 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Alvaro Moreno-Asptia, M.D.
Organization: Mayo Clinic
Phone: 507/284-1159
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01086605     History of Changes
Other Study ID Numbers: N1031
NCCTG-N1031
CDR0000667253 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2011-02021 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA025224 ( U.S. NIH Grant/Contract )
First Submitted: March 12, 2010
First Posted: March 15, 2010
Results First Submitted: December 12, 2016
Results First Posted: February 23, 2017
Last Update Posted: May 8, 2018