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

NCT02360059 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2014-0438NCI-2015-00510
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Breast cancer; Neuropathy; Paclitaxel; Metformin; Metformin ER; Placebo; Sugar pill; Questionnaires; Sensory tests; Fine-motor tests; Surveys

Outcome Measures

Primary Outcomes (1)

• Mean Change in Neuropathy

  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.

  Up to 14 weeks, assessed every 3 weeks ±1 week (T2, T3, T4, T5) during paclitaxel therapy

Study Arms (2)

Metformin Group

EXPERIMENTAL

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; Behavioral: Questionnaires; Other: Sensory and Fine-Motor Tests

Placebo Group

PLACEBO COMPARATOR

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; Behavioral: Questionnaires; Other: Sensory and Fine-Motor Tests

Interventions

Metformin DRUG

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.

Also known as: Metformin ER

Metformin Group

Placebo OTHER

Participants take placebo by mouth twice daily starting 12 days before, and 12 weeks during Paclitaxel treatment.

Also known as: Sugar pill

Placebo Group

Questionnaires BEHAVIORAL

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.

Also known as: Surveys

Metformin Group; Placebo Group

Sensory and Fine-Motor Tests OTHER

Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.

Metformin Group; Placebo Group

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed invasive breast cancer, stage I - IV, treated at Lyndon B. Johnson General Hospital in the Harris Health System.
• Patients = or \> 18 years old and \< 75 years old.
• Patients scheduled to undergo paclitaxel chemotherapy for breast cancer.
• 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.
• 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.
• Patients who speak English and/or Spanish.
• Patients who are willing and able to review, understand, and provide written consent.
• Patients with an Eastern Cooperative Oncology performance status of 0 or 1.

You may not qualify if:

• 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).
• Patients using carbonic anhydrase inhibitors (acetazolamide \[Diamox®\], brinzolamide \[Azopt®\], methazolamide \[Neptazane®\], dorzolamide \[Trusopt®\], pomegranate ellagitannins), cimetidine, or topiramate.
• Patients who are enrolled in another symptom management trial.
• Patients with nerve pathology or clinically identified neuropathy.
• 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.
• 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).
• Patients with intestinal issues, including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• 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.
• Patients with any condition that precludes use of the study medication as determined by the treating physician.
• Patients with a diagnosis of hepatitis or HIV.
• 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.
• Patients who are currently using metformin (eg, Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

Lyndon B. Johnson General Hospital

Houston, Texas, 77026, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Metformin; Sugars; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Carbohydrates; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Dr. David L. Ramirez, Assistant Professor, Breast Medical Oncology
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• David L. Ramirez, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 10, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: August 17, 2017
• Results First Posted: August 17, 2017

Record last verified: 2017-07

Locations

US (1)