A Phase 2 interventional study of pixantrone dimaleate in Breast Cancer, sponsored by Alliance for Clinical Trials in Oncology. Completed at 230 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-05-08.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 2, Interventional, and Treatment
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.
OBJECTIVES:
Primary
Secondary
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.
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 46 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Registration and Randomization - Inclusion Criteria
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.
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
Registration and Randomization - Exclusion Criteria
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)
>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.
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.
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).
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.
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)
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.
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
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
Proportion of Confirmed Tumor Responses (Complete or Partial Response)
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
Time to Disease Progression
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
6-month Progression-free Survival Rate
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
Overall Survival Time
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
Duration of Response
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
Toxicity
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
| Milestone | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) |
|---|---|---|
| Started | 24 | 22 |
| Completed | 24 | 22 |
| Not completed | 0 | 0 |
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.
| proportion | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) |
|---|---|---|
| Proportion of Confirmed Tumor Responses (Complete or Partial Response) | 0.08 (0.01 to 0.27) | 0.05 (0 to 0.24) |
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).
| months | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) |
|---|---|---|
| Time to Disease Progression | 2.8 (1.4 to 7.9) | 2.5 (1.7 to 4.1) |
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).
| proportion | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) |
|---|---|---|
| 6-month Progression-free Survival Rate | 0.375 (0.224 to 0.629) | 0.265 (0.227 to 0.553) |
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.
| months | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) |
|---|---|---|
| Overall Survival Time | 16.8 (9 to NA) | 9.6 (4.7 to NA) |
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.
| months | Arm I/Group A + Arm II/Group B |
|---|---|
| Duration of Response | 5.8 (4.6 to 7.2) |
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.
| Participants | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) |
|---|---|---|
| Toxicity | 16 | 19 |
Collected over 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).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I/Group A | — | 3/24 (12.5%) | 23/24 (95.8%) |
| Arm II/Group B | — | 9/22 (40.9%) | 22/22 (100%) |
| Event | Arm I/Group A | Arm II/Group B |
|---|---|---|
| Neutrophil count decreasedInvestigations | 2/24 | 2/22 |
| White blood cell decreasedInvestigations | 0/24 | 2/22 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 0/24 | 2/22 |
| Disseminated intravascular coagulationBlood and lymphatic system disorders | 0/24 | 1/22 |
| Death NOSGeneral disorders | 0/24 | 1/22 |
| Edema limbsGeneral disorders | 0/24 | 1/22 |
| FatigueGeneral disorders | 0/24 | 1/22 |
| Aspartate aminotransferase increasedInvestigations | 1/24 | 1/22 |
| Blood bilirubin increasedInvestigations | 0/24 | 1/22 |
| Ejection fraction decreasedInvestigations | 1/24 | 1/22 |
| Event | Arm I/Group A | Arm II/Group B |
|---|---|---|
| Neutrophil count decreasedInvestigations | 20/24 | 21/22 |
| FatigueGeneral disorders | 21/24 | 20/22 |
| AnemiaBlood and lymphatic system disorders | 18/24 | 18/22 |
| AlopeciaSkin and subcutaneous tissue disorders | 18/24 | 16/22 |
| NauseaGastrointestinal disorders | 16/24 | 16/22 |
| Skin and subcutaneous tissue disorders - Other, specifySkin and subcutaneous tissue disorders | 12/24 | 8/22 |
| DiarrheaGastrointestinal disorders | 10/24 | 6/22 |
| VomitingGastrointestinal disorders | 9/24 | 9/22 |
| Aspartate aminotransferase increasedInvestigations | 5/24 | 8/22 |
| Platelet count decreasedInvestigations | 5/24 | 8/22 |
| Age, Continuous(years) | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) | Total |
|---|---|---|---|
| Median | 56.5 (42 to 79) | 52.5 (38 to 75) | 55.5 (38 to 79) |
| Sex: Female, Male(Participants) | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) | Total |
|---|---|---|---|
| Female | 23 | 22 | 45 |
| Male | 1 | 0 | 1 |
| Region of Enrollment(participants) | Arm I/Group A (Pixantrone IV Day 1) | Arm II/Group B (Pixantrone IV Days 1, 8, and 15) | Total |
|---|---|---|---|
| United States | 24 | 22 | 46 |
Showing the first 100 of 230 sites.
This study is completed, as verified in Apr 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Alliance for Clinical Trials in Oncology