Pixantrone Dimaleate in Treating Patients With HER2-Negative Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: pixantrone dimaleate
Intervention description: Given IV
Intervention MeSH terms: Pixantrone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2-negative breast cancer; male breast cancer; recurrent breast cancer; stage IV breast cancer; stage IIIC breast cancer

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.
    

Eligibility criteria:

        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.

          5. Patients must have measurable disease as defined in the protocol.

          6. Negative pregnancy test done ≤7 days prior to registration, for women of childbearing
             potential only.

          7. 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

          8. LVEF ≥50% and EKG within institutional normal limits completed ≤22 days prior to
             registration.

          9. ECOG Performance Status (PS) of 0, 1 or 2.

         10. Life expectancy >3 months

         11. Ability to complete questionnaire(s) by themselves or with assistance.

         12. Patient has provided written informed consent

         13. 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)

          2. Stage III or IV invasive cancer (other than breast cancer) in ≤3 years prior to
             registration (with the exception of non-melanoma skin cancer).

          3. HER2 positive breast cancer (3+ by IHC or FISH amplified) breast cancer by ASCO/CAP
             guidelines

          4. Has already received lifetime cumulative treatment with doxorubicin equivalent to >400
             mg/m2.

          5. >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.

          6. 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.

          7. 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).

          8. 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.

          9. 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.).

         10. 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)

         11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements.

         12. 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.

         13. History of allergy or hypersensitivity to drug product excipients or agents chemically
             similar to pixantrone.

         14. 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.