Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and Tumor Necrosis Factor Alpha (TNF-α) Release
Condition: Breast Cancer; Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma, Non-Hodgkin
Intervention: Mesna; Saline; Doxorubicin; Cyclophosphamide
Intervention description: Mesna: 360 mg/m2 in 50 mL normal saline (NS) either on cycle 2 or cycle 1, day 1. Infused over 15 minutes; Saline (used as a placebo) infused over the same time as mesna intervention; 60mg/m2 given IV over 15 minutes after receiving mesna or saline. Can allow for premedications of Ondansetron 8 mg orally, dexamethasone 12 mg orally, Aprepitant 125 mg orally.; 600 mg/m2 IV over 30 minutes. Start 6 hours after doxorubicin started.
Intervention MeSH terms: Cyclophosphamide; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: chemobrain; Oxidative Stress; Mesna

Summary:

      The purpose of this study is to determine whether the drug mesna is able to block a series of
      chemical changes that occur in the blood of patients who receive the chemotherapy medicine
      doxorubicin. The researchers believe these blood chemical changes may the cause of "cloudy
      thinking" or "chemobrain" that are reported by some patients receiving chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

        Participants must have histologically or cytologically confirmed breast cancer or
        non-hodgkin lymphoma and independent of protocol eligibility be determined to require one
        of the chemotherapy regimens listed below

        Participants must require as standard-of-care treatment a chemotherapy regimen that
        includes one of the following combinations:

          -  doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2;

          -  doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, and docetaxel 75 mg/m2;

          -  doxorubicin 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (capped at 2
             mg dose), and prednisone 100 mg +/- rituximab 375 mg/m2

        Age >18 years.Because these treatment regimens are rarely used in pediatric oncology,
        children are excluded from this study but will be eligible for future pediatric phase 2
        trials.

        Life expectancy of greater than 6 months.

        Zubrod performance score 2 or better.

        Patients must have normal organ and marrow function as defined below:

          -  leukocytes >3,000/microliter (mcL) (unless due to cancer in marrow)

          -  absolute neutrophil count >1,500/mcL (unless due to cancer in marrow)

          -  platelets >100,000/mcL (unless due to cancer in marrow)

          -  total bilirubin <1.5 X normal institutional limits

          -  Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase
             (SGOT)/Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase (SGPT)
             <2.5 X institutional upper limit of normal

          -  creatinine within normal institutional limits OR

          -  creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
             institutional normal

          -  left ventricular function ≥ 50 % ejection fraction

        Because the standard of care chemotherapy agents are known to be teratogenic, women of
        child-bearing potential and men must agree to use adequate contraception (hormonal or
        barrier method of birth control; abstinence) prior to study entry and for the duration of
        study participation. Should a woman become pregnant or suspect she is pregnant while
        participating in this study, she should inform her treating physician immediately.

        Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

        Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas
        or mitomycin C) prior to entering the study or those who have not recovered from adverse
        events due to agents administered more than 4 weeks earlier.

        Patients may not be receiving any other investigational agents

        Patients with known brain metastases should be excluded from this clinical trial because
        progressive neurologic dysfunction would confound the evaluation of neuro-cognitive
        outcomes.

        History of allergic reactions attributed to compounds of similar chemical or biologic
        composition to mesna or other agents used in the study (ie. sulfur containing drugs
        including "sulfa antibiotics" and celecoxib).

        Patients requiring ongoing pharmacologic treatment of dementia are excluded.

        Uncontrolled intercurrent illness including, but not limited to, ongoing or active
        infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
        arrhythmia, or psychiatric illness/social situations that would limit compliance with study
        requirements.

        Pregnant women are excluded from this study because the chemotherapy agents have known
        teratogenic or abortifacient effects. Because there is a potential risk for adverse events
        in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding
        should be discontinued if the mother is treated with chemotherapy.

        HIV-positivity is NOT a specific exclusion criteria.