Study of Pralatrexate in Female Patients With Previously-treated Breast Cancer
Condition: Breast Cancer; Breast Tumors; Neoplasms, Breast; Cancer of the Breast; Human Mammary Carcinoma
MeSH terms: Breast Neoplasms
Intervention: Pralatrexate Injection; Vitamin B12; Folic Acid
Intervention description: Intravenous (IV) push administration over 3-5 minutes.
Initial dose: 190 mg/m2
Dose reductions per protocol: 150 mg/m2, 120 mg/m2, and 100 mg/m2 allowed for defined toxicities.
Administered on days 1 and 15 of a 4-week cycle (every 2 weeks) until criteria for discontinuation per the protocol are met.; 1 mg intramuscular injection
Administered within 10 weeks prior to first dose of pralatrexate, every 8-10 weeks throughout the study and for at least 30 days after the last dose of pralatrexate.; 1.0-1.25 mg orally
Administered daily for at least 7 days prior to first dose of pralatrexate, throughout the study and for at least 30 days after the last dose of pralatrexate.
Intervention MeSH terms: Vitamins; Folic Acid; Vitamin B 12; Vitamin B Complex; 10-deazaaminopterin; Aminopterin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Female; Advanced; Metastatic

Summary:

      The purpose of this study is to determine the efficacy (ability to provide a beneficial
      treatment of the disease) of pralatrexate for the treatment of female patients with advanced
      or metastatic breast cancer who have failed prior chemotherapy. Patients will receive vitamin
      B12 and folic acid supplementation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HER-2 negative advanced or metastatic breast cancer

          -  Disease has become worse after at least 1 prior chemotherapy regimen for advanced or
             metastatic disease

          -  Advanced or metastatic disease resistant to both a taxane and an
             anthracycline-containing chemotherapy regimen, or resistant to taxanes and for whom
             further anthracycline therapy is not indicated

          -  Patients with controlled brain metastases must have finished receiving radiation
             therapy and if on corticosteroids, be on a stable or tapering dose of ≤ 10 mg/day of
             prednisone or equivalent for at least 28 days prior to study entry

          -  Measurable disease

          -  Female 18 years of age or older

          -  Performance status less than or equal to 2

          -  Life expectancy of more than 3 months

          -  Blood, liver and kidney laboratory test results that meet protocol requirements

          -  Patients must have a negative serum pregnancy test within 14 days before enrollment
             and agree to use medically acceptable and effective birth control from enrollment
             until at least 30 days after the last dose of pralatrexate. Patients who are
             postmenopausal for at least 1 year (more than 12 months since last menses) or are
             surgically sterilized do not require this test.

          -  Willing to attend visits for repeat dosing and follow up

          -  Give written informed consent

        Exclusion Criteria:

          -  Patients with only bone metastasis

          -  Patients with a single metastatic site without histological proof that the lesion is
             metastatic breast cancer

          -  Patients with inflammatory breast cancer

          -  Treatment with systemic chemotherapy, hormone therapy, radiation therapy, or other
             investigational therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C) prior
             to enrollment, except for the following:

               -  Bisphosphonates, if ongoing

               -  Prior treatment with methotrexate

               -  Prior treatment with anti-angiogenics within 6 months prior to enrollment

          -  Have received more than 2 prior chemotherapy regimens (more than 3 if one of the
             treatments was neoadjuvant or adjuvant chemotherapy)

          -  Have previously received pralatrexate

          -  Have received more than the allowed maximum total dose of anthracycline

          -  Prior radiation therapy on more than 30% of bone marrow reserve or prior bone
             marrow/stem cell transplantation

          -  Congestive heart failure Class III/IV

          -  Uncontrolled hypertension (high blood pressure)

          -  Active infection or any serious medical condition, which would impair the ability of
             the patient to receive protocol treatment

          -  Females who are pregnant or breastfeeding

          -  Major surgery within 14 days of enrollment

          -  Another active cancer in addition to advanced or metastatic breast cancer, except well
             treated in situ cervical cancer and basal cell skin cancer

          -  Dementia or other altered mental status that would prevent the patient from
             understanding and giving informed consent or limit her ability to follow the study
             requirements

          -  Patients who are human immunodeficiency virus (HIV)-positive and have a CD4 count of
             less than 100 mm3 or detectable viral load within past 3 months and is receiving
             anti-retroviral therapy

          -  Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) who have a detectable
             viral load or immunological evidence of chronic active disease or receiving/requiring
             antiviral therapy