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Metformin for Reduction of Paclitaxel-Related Neuropathy in Patients With Breast Cancer

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ClinicalTrials.gov Identifier: NCT02360059
Recruitment Status : Terminated (Low Accrual)
First Posted : February 10, 2015
Results First Posted : August 17, 2017
Last Update Posted : August 17, 2017
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Metformin Other: Placebo Behavioral: Questionnaires Other: Sensory and Fine-Motor Tests Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Metformin for Reduction of Paclitaxel Treatment-Related Neuropathy in Patients With Breast Cancer: A Randomized Pilot Study
Actual Study Start Date : October 2015
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Metformin Group

Participants take 1,000 mg Metformin by mouth twice daily for 12 weeks during Paclitaxel treatment.

Adaptation phase begins 12 days prior to the start of the Paclitaxel therapy. During this phase, study medication dose starts at 500 mg daily for 5 days, followed by 500 mg twice daily for 5 days, followed by the desired dose of 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.

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.

Drug: Metformin
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.
Other Name: Metformin ER

Behavioral: Questionnaires
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.
Other Name: Surveys

Other: Sensory and Fine-Motor Tests
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.

Placebo Comparator: Placebo Group

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.

Other: Placebo
Participants take placebo by mouth twice daily starting 12 days before, and 12 weeks during Paclitaxel treatment.
Other Name: Sugar pill

Behavioral: Questionnaires
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.
Other Name: Surveys

Other: Sensory and Fine-Motor Tests
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.




Primary Outcome Measures :
  1. Mean Change in Neuropathy [ Time Frame: Up to 14 weeks, assessed every 3 weeks ±1 week (T2, T3, T4, T5) during paclitaxel therapy ]
    Change in neuropathy as assessed with the chemotherapy-induced peripheral neuropathy (CIPN) survey QLQ-CIPN20 between T1 and T5 where difference in mean area under the curve (AUC) between groups reported. The AUC for response from T1 to T5 is computed by fitting a series of trapezoids to the QLQ-CIPN20 data assessed at T1, T2, T3, T4, and T5, respectively, and summing up their areas [AUC calculated - base of a trapezoid corresponds to the number of days between assessments, and the heights correspond to two adjoining symptom responses, number of trapezoids depends on number of symptom assessments and sum of area for all trapezoids represents AUC of particular participant]. QLQ-CIPN20 contains 20 items assessing sensory (9 items), motor (8 items), and autonomic symptoms (3 items) using a 4-point Likert scale (1 = "not at all," 2 = "a little," 3 = "quite a bit," and 4 = "very much") with the higher score denoting more symptom burden.



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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02360059


Locations
United States, Texas
Lyndon B. Johnson General Hospital
Houston, Texas, United States, 77026
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: David L. Ramirez, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02360059     History of Changes
Other Study ID Numbers: 2014-0438
NCI-2015-00510 ( Registry Identifier: NCI CTRP )
First Posted: February 10, 2015    Key Record Dates
Results First Posted: August 17, 2017
Last Update Posted: August 17, 2017
Last Verified: July 2017

Keywords provided by M.D. Anderson Cancer Center:
Breast cancer
Neuropathy
Paclitaxel
Metformin
Metformin ER
Placebo
Sugar pill
Questionnaires
Sensory tests
Fine-motor tests
Surveys

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Metformin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs