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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Mara Chambers, University of Kentucky
ClinicalTrials.gov Identifier:
NCT01205503
First received: September 17, 2010
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Chemobrain
Drug: Mesna
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Blinded Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and TNF-α Release

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Primary Outcome Measures:
  • Plasma protein oxidation and TNF-α levels in patients receiving doxorubicin containing chemotherapy [ Time Frame: prior to and 3 hours post doxorubicin ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: September 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Cycle 1 saline; cycle 2 mesna
Saline administered prior to and 3 hours post doxorubicin infusion during 1st cycle Mesna administered prior to and 3 hours post doxorubicin infusion during 2nd cycle
Drug: Mesna
Mesna: 360 mg/m2 in 50 mL NS cycle 2 day or cycle 1 day 1
Cycle 1 Mesna ; Cycle 2 saline
Mesna administered prior to and 3 hours post doxorubicin infusion during 1st cycle Saline administered prior to and 3 hours post doxorubicin infusion during 2nd cycle
Drug: Mesna
Mesna: 360 mg/m2 in 50 mL NS cycle 2 day or cycle 1 day 1

Detailed Description:

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.

  Eligibility

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01205503

Locations
United States, Kentucky
University of Kentucky Markey Cancer Center
Lexington, Kentucky, United States, 40536
Sponsors and Collaborators
Mara Chambers
Investigators
Principal Investigator: Mara Chambers, M.D. Markey Cancer Center
  More Information

No publications provided

Responsible Party: Mara Chambers, Principal Investigator, University of Kentucky
ClinicalTrials.gov Identifier: NCT01205503     History of Changes
Other Study ID Numbers: 10-0431-F1V
Study First Received: September 17, 2010
Last Updated: June 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Kentucky:
Chemobrain

Additional relevant MeSH terms:
Doxorubicin
Liposomal doxorubicin
Mesna
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014