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Randomized, Blinded Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and TNF-α Release

Phase 2
18 Years
Open (Enrolling)

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Trial Information

Randomized, Blinded Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and TNF-α Release

Patients with lymphoma and breast cancer receiving chemotherapy regimens that include
anthracycline drugs, such as doxorubicin, are at risk for developing cognitive and cardiac
impairment. This potential cognitive impairment is refered to as "chemobrain" by some
patients. We have demonstrated in mice that the drug mesna, which is used to prevent other
complications of other chemotherapy drugs, prevents certain types of doxorubicin-induced
damage of blood proteins. Blocking doxorubicin's damage of these blood proteins has blunted
or prevented the subsequent markers of neurologic and cardiac injury in mice. This clinical
trial will determine if mesna prevents doxorubicin-induced damage of blood proteins in
cancer patients, and may establish if blood protein injury is the first step in
anthracycline-induced cognitive and cardiac dysfunction and if using the drug mesna can
blunt or prevent these changes in blood markers of injury for patients with cancer.

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

Life expectancy of greater than 6 months.

Zubrod performance status 2 or better.

Patients must have normal organ and marrow function as defined below:

- leukocytes >3,000/mcL (unless due to cancer in marrow)

- absoluteneutrophil 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

- AST(SGOT)/ALT(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

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.

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Plasma protein oxidation and TNF-α levels in patients receiving doxorubicin containing chemotherapy

Outcome Time Frame:

prior to and 3 hours post doxorubicin

Safety Issue:


Principal Investigator

John Hayslip, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Markey Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

September 2010

Completion Date:

September 2014

Related Keywords:

  • Chemobrain
  • Chemobrain



University of Kentucky Lexington, Kentucky  40536-0098
University of Kentucky Markey Cancer Center Lexington, Kentucky  40536