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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01086605
First received: March 12, 2010
Last updated: June 19, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Breast Cancer
Drug: pixantrone dimaleate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Two Doses of Pixantrone in Patients With Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of confirmed tumor responses (complete or partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to disease progression [ Designated as safety issue: No ]
  • 6-month progression-free survival rate [ Designated as safety issue: No ]
  • Overall survival time [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Overall quality of life [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE [ Designated as safety issue: Yes ]

Estimated Enrollment: 56
Study Start Date: May 2010
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

OBJECTIVES:

Primary

  • To assess the proportion of confirmed tumor responses in patients with HER2-negative metastatic breast cancer treated with pixantrone dimaleate.

Secondary

  • To describe the distribution of progression-free survival (PFS) times of patients treated with this drug.
  • To assess the 6-month PFS rate in patients treated with this drug.
  • To describe the overall survival of patients treated with this drug.
  • To assess the adverse event profile of this drug in these patients.
  • To evaluate the quality of life and patient-reported symptoms of patients treated with this drug.
  • To evaluate quantitative and qualitative changes of circulating tumor cells after pixantrone dimaleate therapy. (Correlative study)
  • To bank blood and tissue samples for future evaluation of pharmacogenetic and/or proteomic markers. (Correlative study)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the breast

    • Metastatic disease
  • Must have been treated in neoadjuvant, adjuvant, or metastatic setting with anthracycline and/or taxane
  • Must have received 2-3 prior chemotherapy regimens

    • Received ≤ 2 prior chemotherapy regimens in the metastatic setting if no prior neoadjuvant or adjuvant chemotherapy
    • Received ≥ 1 prior chemotherapy regimen in the metastatic setting if prior neoadjuvant or adjuvant chemotherapy
  • Measurable disease
  • HER2-negative disease
  • No active brain metastasis, including leptomeningeal involvement

    • CNS metastasis controlled by prior surgery and/or radiotherapy allowed

      • There must be ≥ 2 months of no symptoms or evidence of progression
      • Patient must discontinue corticosteroid to control brain edema
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • ECOG performance status 0-2
  • Life expectancy > 3 months
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 5 times ULN
  • Serum creatinine ≤ 1.5 times ULN
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • LVEF ≥ 50% and EKG normal within the past 22 days
  • No other prior stage III or IV invasive cancer within the past 3 years except curatively treated nonmelanoma skin cancer
  • No uncontrolled hypertension (BP > 160/90 mm Hg on ≥ 2 occasions)

    • Patients on any stable new regimen or adjusted anti-hypertensive medications allowed provided BP < 140/90 mmHg for ≥ 3 different observations in ≥ 14 days
  • No clinically significant cardiovascular or cerebrovascular disease, including any history of the following:

    • Myocardial infarction
    • Unstable angina pectoris
    • NYHA class II-IV congestive heart failure
    • Uncontrolled or clinically significant cardiac arrhythmia

      • Controlled atrial fibrillation allowed
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • No co-morbid systemic illnesses or other severe concurrent disease that, 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 drug
  • No history of allergy or hypersensitivity to drug product excipients or agents chemically similar to pixantrone dimaleate

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No more than 3 prior chemotherapy regimens for breast cancer

    • This number includes neoadjuvant or adjuvant chemotherapy, if given
    • If neoadjuvant or adjuvant chemotherapy has been giving it counts as 1 regimen
  • Unlimited prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting allowed
  • Lifetime cumulative treatment with doxorubicin ≤ 400 mg/m²
  • More than 3 weeks since prior major surgery, chemotherapy, or immunologic therapy
  • At least 4 weeks since prior bevacizumab
  • No prior radiotherapy within the past 4 weeks and recovered

    • Radiotherapy to non-target lesions allowed
    • Prior radiotherapy to a target lesion allowed provided there has been clear progression of the lesion since completion of radiotherapy
    • Palliative single dose of radiotherapy allowed
  • No other concurrent chemotherapy, biologic agents, or radiotherapy
  • No concurrent investigational procedures or investigational therapies

    • Trials related to symptom management that do not employ hormonal treatments or treatments that may block the path of the targeted agents used in this trial may be allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01086605

  Show 230 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Principal Investigator: Kostandinos Sideras, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Kostandinos Sideras, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT01086605     History of Changes
Other Study ID Numbers: CDR0000667253, NCCTG-N1031
Study First Received: March 12, 2010
Last Updated: June 19, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
HER2-negative breast cancer
male breast cancer
recurrent breast cancer
stage IV breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pixantrone
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 22, 2014