Metformin for Reduction of Paclitaxel-Related Neuropathy in Patients With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Metformin; Placebo; Questionnaires; Sensory and Fine-Motor Tests
Intervention description: Metformin dose starts at 500 mg daily for 5 days, followed by 500 mg twice daily for 5 days, followed by 1,000 mg twice daily for 2 days. Participants reach required study medication dose of 2,000 mg daily 2 days prior to commencement of Paclitaxel therapy and continue this dose for remainder of intervention.; Participants take placebo by mouth twice daily starting 12 days before, and 12 weeks during Paclitaxel treatment.; Questionnaires completed about numbness and/or symptoms about 2 weeks before start of Paclitaxel, 1 -2 days before Paclitaxel, every week while taking Paclitaxel, and at end of study visit. At week 12, questionnaire completed regarding satisfaction with Paclitaxel.; Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.
Intervention MeSH terms: Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: Breast cancer; Neuropathy; Paclitaxel; Metformin; Metformin ER; Placebo; Sugar pill; Questionnaires; Sensory tests; Fine-motor tests; Surveys

Summary:

      The goal of this clinical research study is to learn if metformin can help to control nerve
      damage (loss of motor or sensory function) that may be caused by treatment with paclitaxel in
      patients with breast cancer.

      In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks
      like the study drug, but it is not designed to treat any disease or illness. It is designed
      to be compared with a study drug to learn if the study drug has any real effect.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologically confirmed invasive breast cancer, stage I - IV, treated
             at Lyndon B. Johnson General Hospital in the Harris Health System.

          2. Patients = or > 18 years old and < 75 years old.

          3. Patients scheduled to undergo paclitaxel chemotherapy for breast cancer.

          4. Patients with adequate renal function, as evidenced in laboratory values = or < 3
             months old: epidermal growth factor receptor (eGFR) = or > 60 mL/min/1.73m2.

          5. Patients with adequate hepatic function per institutional testing standards, as
             evidenced in laboratory values = or < 3 months old: (1) The screening results for
             total bilirubin must be < 1.5 times the upper limit of normal. (2) The screening
             results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must
             be < 2 times the upper limit of normal.

          6. Patients who speak English and/or Spanish.

          7. Patients who are willing and able to review, understand, and provide written consent.

          8. Patients with an Eastern Cooperative Oncology performance status of 0 or 1.

        Exclusion Criteria:

          1. Patients with a history of or known diagnosis of diabetes according to national
             guidelines (fasting plasma glucose > or = 126 mg/dL or random plasma glucose > or =
             200 mg/dL), as evidenced in laboratory values < or = 3 months old).

          2. Patients using carbonic anhydrase inhibitors (acetazolamide [Diamox®], brinzolamide
             [Azopt®], methazolamide [Neptazane®], dorzolamide [Trusopt®], pomegranate
             ellagitannins), cimetidine, or topiramate.

          3. Patients who are enrolled in another symptom management trial.

          4. Patients with nerve pathology or clinically identified neuropathy.

          5. Patients with a history of clinically significant cutaneous drug reaction,
             hypersensitivity reaction, anaphylaxis, or any other serious adverse reaction to the
             medication used in the study.

          6. Patients with any condition associated with increased risk of metformin-associated
             lactic acidosis (e.g., congestive heart failure defined as New York Heart Association
             Class III or IV functional status, history of acidosis of any type).

          7. Patients with intestinal issues, including malabsorption syndrome, disease
             significantly affecting gastrointestinal function, or resection of the stomach or
             small bowel.

          8. Patients who are pregnant are excluded. Pre-menopausal women must have a negative
             pregnancy test. Patients that are post menopausal, or that have had a hysterectomy do
             not need to have a pregnancy test.

          9. Patients with any condition that precludes use of the study medication as determined
             by the treating physician.

         10. Patients with a diagnosis of hepatitis or HIV.

         11. Patients currently receiving or scheduled to receive a chemotherapy infusion other
             than Adriamycin/Cyclophosphamide prior to initiation of the metformin adaptation phase
             are not eligible. Patients who are receiving Adriamycin/Cyclophosphamide must be
             scheduled to be at least 8 days post-chemotherapy infusion prior to initiation of the
             metformin adaptation phase in order to be eligible.

         12. Patients who are currently using metformin (eg, Fortamet, Glucophage, Glucophage XR,
             Glumetza, Riomet).